Table of Contents:

• Taxonomy Information
• Lifecycle Information
• Genome Information
• Biosafety Information
• Culturing Information
• Epidemiology Information
• Diagnostic Tests Information
• Infected Hosts Information
• Phinet: Pathogen-Host Interaction Network
• Lab Animal Pathobiology & Management
• References
• Data Provenance and Curators

1. Species:
   1. Junin virus (Website 2):
      1. Common Name: Junin virus
      2. GenBank Taxonomy No.: 11619
      3. Description: Argentine hemorrhagic fever (AHF), first described in 1955, is characterized by vascular, renal, hematological, neurological, and immunological alterations, with a case fatality rate of 15-30% in untreated individuals. The etiological agent of AHF is Junin virus (JUN), which was initially isolated in 1958 and confirmed in 1959. Subsequently, JUN was serologically assigned to the Tacaribe group of viruses, which belongs for the family Arenaviridae, genus Arenavirus. Arenaviruses are rodent-borne, enveloped, single-stranded, ambisense RNA viruses with a segmented genome(Garcia et al., 2000).

1. Junin Virus Information
   1. Stage Information:
      1. Virion:
         • Size: Morphologically, arenavirus virions consist of enveloped particles that vary in diameter from approximately 60 to more than 300 nm, with a mean particle size of 92 nm as determined by electron microscopy.
         • Shape: The virions are approximately spherical, enveloped particles that range in diameter from 50 to 300 nm.. The surface of the virion is smooth with T-shaped spikes, composed of viral glycoproteins, extending 7-10 nm from the envelope.

1. Genome of Junin virus
   1. Description: The arenavirus genome consists of two single-stranded RNA molecules, designated L and S, that contain essentially nonoverlapping sequence information. There are minor differences in the lengths of the genomic RNA segments for the individual viruses (L approximately 7,200 bases and S approximately 3,400 bases), but the general organization of the viral genomes, based on current sequence information, is well preserved across the virus family(Southern, 1996). The genomic RNA consists of two segments, S (3.4 k) and L (7.2 kb), both of which are arranged in an ambisense orientation. The S segment encodes the nucleocapsid protein (NP) in negative, antimessage sense at the 3'-end and the viral glycoprotein precursor, GP-C in message sense at the 5'-end. The L RNA segment contains the L protein (polymerase) gene at the 3'-end in negative polarity and the zinc-binding (Z) protein at the 5'-end in message polarity. Posttranslational modification of the cell-associated GP-C precursor yields the structural glycoproteins GP-1 (44 kd) and GP-2 (35 kd), which are assembled into a tetrameric virion spike. GP-1 contains determinants that interact with viral receptors and is recognized by neutralizing antibody. GP-2 contains sites that promote acid-dependent membrane fusion necessary for viral entry. The nucleocapsid protein is an internal RNA-binding protein that complexes with genomic RNA(Peters et al., 1996).
   2. S Segment
      1. Size: S RNA molecule of Junin virus. The complete sequence is 3400 bp(Ghiringhelli et al., 1991).
      2. Gene Count: 2 genes in the S segment(Garcia et al., 2000).
      3. Description: The arenavirus genome is composed of two RNA species. The large (L) segment (about 7200 nucleotides in length) encodes the virus polymerase (L protein) and a small zinc binding protein. The small RNA segment (S) (ca. 3400 nucleotides in length) encodes the nucleocapsid (NP) protein and the glycoprotein precursor, GPC, of two viral glycoproteins, GP1 and GP2(Garcia et al., 2000).
   3. L Segment
      1. Size: L RNA molecule of Junin virus is about 7200 nucleotides in length(Garcia et al., 2000).
      2. Gene Count: 2 genes in the L segment(Garcia et al., 2000).
      3. Description: The arenavirus genome is composed of two RNA species. The large (L) segment (about 7200 nucleotides in length) encodes the virus polymerase (L protein) and a small zinc binding protein. The small RNA segment (S) (ca. 3400 nucleotides in length) encodes the nucleocapsid (NP) protein and the glycoprotein precursor, k GPC, of two viral glycoproteins, GP1 and GP2(Garcia et al., 2000).

1. Biosafety information for Junin virus
   1. Level: Like Lassa virus, Junin, Machupo, Guanarito, and Sabia viruses are infectious by aerosol and the human and rodent specimens should be processed with appropriate precautions in BSL 4 laboratories(Buchmeier et al., 2001).
   2. Precautions: Strict isolation and containment measures are not justified, because AHF is not usually contagious, although a few well-documented instances of interhuman transmission have been found. They can be prevented by avoiding intimate contacts with patients and by properly handling, decontaminating, and disposing of blood and secretions(Webb and Maiztegui, 1988). Because of the hazards inherent in working with Class IV viruses, specific diagnosis should ideally be made in laboratories with special containment facilities(Shepherd, 1988).

1. Vero Cell Culturing :
   1. Description: The best method to isolate Marburg, Ebola, and pathogenic arenaviruses is inoculation of Vero cells, then immunofluorescence or other immunologically-specific testing of inoculated cells for specific viruses at intervals(Jahrling, 1989). Historically, Machupo and Junin viruses were isolated by ic inoculation of newborn hamsters and mice, respectively, but Vero cells are as sensitive and much easier than animals to manage in a P-4 containment. Furthermore, Vero cells permit isolation and identification in 1-5 days, a big advantage over animals, which require 7-20 days of incubation for illness to develop(Jahrling, 1989). Co-cultivation of peripheral leukocytes, isolated by hypaque-ficol separation, with susceptible cells (usually Vero) has increased the isolation frequency of Junin virus(Jahrling, 1989). Detection of viremia was attempted by three different methods in 30 cases of Argentine hemorrhagic fever (AHF). Cocultivation of peripheral blood mononuclear cells (PBMC) with Vero cell monolayers was the most sensitive, detecting Junin virus (JV) in 96% of the cases. Inoculation of whole blood into suckling mice and on Vero cells rendered 53 and 46% of positive isolations, respectively. The results presented suggest that PBMC are infected with JV during the acute period of AHF. JV was isolated with decreasing frequency up to 3 days after treatment with immune plasma, but no virus was recovered from PBMC during early convalescence(Ambrosio et al., 1986).
   2. Medium: Vero E6 (monkey kidney fibroblast) and BHK (baby hamster kidney fibroblasts) were grown in Eagle's minimum essential medium (MEM) containing 5% fetal bovine serum and penicillin G 100 U/ml, streptomycin 100 ug/ml and amphotericin B 0.25 ug/ml. Maintenance medium consisted of MEM supplemented with 1.5% fetal bovine serum and antibiotics(Ellenberg et al., 2002).
   3. Note: Isolation in cell culture monolayers (Vero, BHK), in combination with immunohistochemical procedures, such as immunofluorescence (IF) or peroxidase-antiperoxidase (PAP), gives positive results in 1 to 3 days(Webb and Maiztegui, 1988). Virus can be isolated from the blood of viremic patients from 2 to 12 days after onset and most often between 3 and 8. In fatal cases, virus can be isolated from postmortem spleen, kidney, and clotted blood(Shepherd, 1988).

1. Outbreak Locations:
   1. Since the emergence of Argentine hemorrhagic fever (AHF), a progressive geographic expansion of epidemic outbreaks has been observed. In 1958, human cases were limited to an area of 16,000 km(2) in the north of Buenos Aires province. Currently, the endemo-epidemic area covers approximately 150,000 km(2), reaching north of Buenos Aires, south of Santa Fe, southeast of Cordoba, and northeast of La Pampa provinces. At present, the human population at risk is estimated to be around 5 million(Garcia et al., 2000).
2. Transmission Information:
   1. From: Calomys(Salazar-Bravo et al., 2002). , To: Human(Salazar-Bravo et al., 2002). , With Destination:Human(Website 10). (Salazar-Bravo et al., 2002)
      Mechanism: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 10).
   2. From: Akodon azarae(Salazar-Bravo et al., 2002). , To: Human(Salazar-Bravo et al., 2002). , With Destination:Human(Website 10). (Salazar-Bravo et al., 2002)
      Mechanism: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 10).
   3. From: Mus musculus(Salazar-Bravo et al., 2002). , To: Human(Salazar-Bravo et al., 2002). , With Destination:Human(Website 10). (Salazar-Bravo et al., 2002)
      Mechanism: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of the rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 10).
3. Environmental Reservoir:
   1. Rodent(Salazar-Bravo et al., 2002, Vitullo et al., 1987):
      1. Description: Junin virus, the etiological agent of Argentine hemorrhagic fever (AHF), has most commonly been isolated from the organs and body fluids of three species of rodents, Calomys musculinus, C. laucha, and Akodon azarae. In addition, the virus has been isolated from other rodent species such as Mus musculus and Oligoryzomys flavescens. The vesper mouse, Calomys musculinus, is considered the primary reservoir because it was the most commonly trapped rodent in the endemic area, and because persistent viremia and virus shedding via saliva was found both in naturally and laboratory-infected animals(Salazar-Bravo et al., 2002).
      2. Survival: The effect of infection with Junin virus on growth and reproduction of its natural reservoir, Calomys musculinus, was studied. Eighty-five C. musculinus were inoculated intranasally at birth with 100 TCID50 of Cba An 9446 strain of Junin virus and observed for 480 days. No clinical signs of neurologic illness were registered. Infected animals showed an increased mortality rate of up to 70% between days 24-40 post-infection. This period of high mortality was preceded by low weight gain during lactation and registered until 60 days. From day 14 post-infection until day 480, Junin virus was recovered from blood, urine, and oral swab in all animals checked at any time. By day 480 post-infection, 100% of survivors showed widespread viral dissemination in brain, spleen, kidneys, and salivary glands. There was marked reduction in reproductive efficiency among infected animals. Out of 15 mating pairs, 2 (13.3%) littered at least once compared to 60% in the control group. The reduction of fertility and the altered survival rate of Junin virus-infected C. musculinus indicate that vertical transmission mechanisms per se are insufficient to maintain the infection in successive generations in the absence of horizontal transmission(Vitullo et al., 1987).
4. Intentional Releases:
   1. Intentional Release Information:
      1. Emergency Contact: If clinicians feel that VHF is a likely diagnosis, they should take two immediate steps: 1) isolate the patient, and 2) notify local and state health departments and CDC(MMWR, 1988). Report incidents to state health departments and the CDC (telephone {404} 639-1511; from 4:30 p.m. to 8 a.m., telephone {404} 639-2888). Information on investigating and managing patients with suspected viral hemorrhagic fever, collecting and shipping diagnostic specimens, and instituting control measures is available on request from the following persons at Centers for Disease Control (CDC) in Atlanta, Georgia; for all telephone numbers, dial 404-639 + extension: Epidemic Intelligence Service (EIS) Officer, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases (ext. 1344); Chief, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases: Joseph B. McCormick, M.D. (ext. 3308); Senior Medical Officer, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases: Susan P. Fisher-Hoch, M.D. (ext. 3308); Director, Division of Viral Diseases, Center for Infectious Diseases (ext. 3574). After regular office hours and on weekends, the persons named above may be contacted through the CDC duty officer (ext. 2888)(MMWR, 1988).
      2. Delivery Mechanism: The VHF agents are all highly infectious via the aerosol route, and most are quite stable as respirable aerosols. This means that they satisfy at least one criterion for being weaponized, and some clearly have the potential to be biological warfare threats. Most of these agents replicate in cell culture to concentrations sufficiently high to produce a small terrorist weapon, one suitable for introducing lethal doses of virus into the air intake of an airplane or office building. Some replicate to even higher concentrations, with obvious potential ramifications. Since the VHF agents cause serious diseases with high morbidity and mortality, their existence as endemic disease threats and as potential biological warfare weapons suggests a formidable potential impact on unit readiness. Further, returning troops may well be carrying exotic viral diseases to which the civilian population is not immune, a major public health concern(Website 8).
      3. Containment: Patients with VHF syndrome generally have significant quantities of virus in their blood, and perhaps in other secretions as well (with the exceptions of dengue and classic hantaviral disease). Well-documented secondary infections among contacts and medical personnel not parenterally exposed have occurred. Thus, caution should be exercised in evaluating and treating patients with suspected VHF syndrome. Over-reaction on the part of medical personnel is inappropriate and detrimental to both patient and staff, but it is prudent to provide isolation measures as rigorous as feasible. At a minimum, these should include the following: stringent barrier nursing; mask, gown, glove, and needle precautions; hazard-labeling of specimens submitted to the clinical laboratory; restricted access to the patient; and autoclaving or liberal disinfection of contaminated materials, using hypochlorite or phenolic disinfectants. For more intensive care, however, increased precautions are advisable. Members of the patient care team should be limited to a small number of selected, trained individuals, and special care should be directed toward eliminating all parenteral exposures. Use of endoscopy, respirators, arterial catheters, routine blood sampling, and extensive laboratory analysis increase opportunities for aerosol dissemination of infectious blood and body fluids. For medical personnel, the wearing of flexible plastic hoods equipped with battery-powered blowers provides excellent protection of the mucous membranes and airways(Website 8).

1. Organism Detection Test:
   1. Electron Microscopy :
      1. Description: When the identity of a VHF agent is totally unknown, isolation in cell culture and direct visualization by electron microscopy, followed by immunological identification by immunohistochemical techniques is often successful(Website 8).
   2. IFA test :
      1. Description: The IFA test is the preferred method for serological diagnosis of Argentinean hemorrhagic fever (AHF). Antibodies are detected earlier by IFA than by CF and, in addition, the number of seroconversion detected is greater by the former test. Even so, seroconversion occurs relatively late, and it may be necessary to test specimens up to 30 or 60 days after onset to obtain serological diagnosis(Shepherd, 1988).
   3. Intracerebral inoculation :
      1. Description: Isolation is made by intracerebral inoculation of 1- to 3-day-old mice or by intracerebral or intraperitoneal inoculation of guinea pigs. Mice appear sick 8 to 10 days after inoculation(Shepherd, 1988).
2. Immunoassay Test:
   1. Complement fixation :
      1. Description: The complement fixation (CF) test is rarely used now, although historically it was the method of choice for detection and presumptive identification of the arenaviruses. The CF test was supplanted by immunofluorescence procedures which became generally accepted.
   2. Complement-Enhanced, Plaque-Reduction Neutralization Test :
      1. Description: A refined, complement-enhanced, plaque-reduction neutralization test was developed for measuring neutralizing antibodies against Junin (Argentine hemorrhagic fever) virus. The assay measured neutralizing antibodies after natural as well as vaccine-induced Junin virus infections. Among vaccinated individuals, titers were 2-4-fold higher than those obtained with conventional assays, without loss of specificity. Enhanced sensitivity was achieved by using a standardized complement source (vs human or animal serum) for virus dilution, incubation of virus-serum mixtures at 36 degrees C for 2 h (vs overnight at 4 degrees C) prior to plaque assay, control of age and density of cell monolayers, and variation in overlay conditions(Barrera Oro et al., 1990).
   3. Antigen capture ELISA :
      1. Description: Antigen capture ELISA allowed detection of viral antigen in blood, serum, or tissue homogenates. These tests could be used in acute diagnosis of patients suspected of Junin, Machupo. Sabia, and Guanarito and are often the first available diagnostic result in rapidly fatal cases when patients died before antibody appearance(Peters et al., 1996).
   4. ELISA :
      1. Description: The ELISA test is the most useful and practical for rapid detection of IgM or IgG antibodies in a clinical setting and in seroepidemiologic surveys. The antibodies detected by ELISA persist more than 30 years in some cases(Peters et al., 1996). To elaborate a set of serological tests for the diagnosis of Argentine haemorrhagic fever (AHF), an enzyme-linked immunosorbent assay (ELISA) for detection of specific anti-Junin virus (JV) IgG is described, and its performance is compared with that of the plaque reduction neutralization test (PRNT). The reproducibility, sensitivity, specificity, and confidence limits for positive and negative results for ELISA were statistically analyzed. The value of 800 was demonstrated as the lowest positive titer. Titers greater than or equal to 800 varied within one (two-fold) dilution in 95.6% of the tests, while the sensitivity and specificity were 99.2% and 98.8%, respectively. The assay yielded 1% of false positives and 0.05% of false negatives. A comparison of ELISA to PRNT in detecting the seroconversion for JV was studied by the chi square test (comparison of proportions in paired samples) and the K parameter for agreement proportion. Comparison of ELISA to PRNT showed no significant difference in the proportions of positive and negative results of these assays (P less than 0.01), demonstrating an equivalent performance (K = 0.98) in the diagnosis of AHF. In addition, the simplicity and safety of the procedures involved make this ELISA the most suitable test to detect natural human JV infections(Riera et al., 1997).
      2. False Positive: The assay yielded 1% of false positives(Riera et al., 1997).
      3. False Negative: The assay yielded 0.05% of false negatives(Riera et al., 1997).
   5. Plaque Reduction Neutralization :
      1. Description: Neutralization tests (Nt) for these viruses vary in efficacy; depending on the virus. Neurtralization tests range from very sensitive and reliable (e.g. Junin and Machupo), through moderately insensitive but reliable (Lassa and LCM), to totally unreliable (Marburg and Ebola). The common denominator in all Nt tests is measurement of inhibition of viral replication by reaction with immune serum(Jahrling, 1989). For New World arenaviruses (Junin and Machupo), the usual test is a plaque reduction Nt using Vero cells and the serum dilution-constant virus format. The serum dilution calculated by (probit analysis) to reduce the control number of plaques by 50% (PRN-50) is usually taken as the endpoint, although some laboratories use 80% reduction (PRN-80). The PRN-80 is used to distinguish Junin virus from Machupo virus(Jahrling, 1989).
   6. Indirect Immunofluorescence Antibody (IIF) Test :
      1. Description: The IIF test is clearly the method of choice in most laboratories for detecting recent infections with Marburg, Ebola, and the arenaviruses. Antibodies measured by the IFA test are usually the first to appear, often becoming detectable within the first few days of hospitalization for Lassa virus, within 10 days of onset for Marburg and Ebola viruses, and somewhat later for Junin and Machupo viruses. Presence of specific IgM antibodies or a rising IFA titer is a presumptive diagnosis of acute infection. IgM antibodies measure by IIF decline to undetectable titers within several months, while IgG antibodies persist at least several years(Jahrling, 1989).
3. Nucleic Acid Detection Test:

1. Human
   1. Taxonomy Information:
      1. Species:
         1. Homo sapiens (Website 9):
            • Common Name: Homo sapiens
            • GenBank Taxonomy No.: 9606
            • Description: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 10).
   2. Infection Process:
      1. Infectious Dose: 1 -10 organisms(Franz et al., 1997),
      2. Description: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 10),
   3. Disease Information:
      1. Argentine hemorrhagic fever :
         1. Incubation: The disease begins insidiously with fever, myalgia, and malaise after an incubation period of 1-2 weeks (perhaps as long as 3 weeks)(Peters, 2002),
         2. Prognosis:
            During the 2nd week of illness, 70 to 80% of the AHF patients improve rapidly and recover without sequelae after a period of convalescence of 1 to 3 months. During this period, patients have asthenia, hair loss, irritability, and memory changes, but they are transitory and disappear gradually. In the remaining 20 to 30% of the cases, severe hemorrhagic or neurologic manifestations, shock, and/or superimposed bacterial infections appear between 8 to 12 days after the onset of symptoms(Webb and Maiztegui, 1988), Pregnant women in the last trimester are also at increased risk of dying from AHF, and the outlook for the fetus is grave(Peters et al., 1996),
         3. Symptom Information :
            • Syndrome -- Argentine Hemorrhagic Fever :
              • Description: Initial symptoms are fever and myalgia frequently accompanied by mild hypotension, conjunctivitis, and petechiae in the axilla, soft palate, and gingival margin. Neurological signs including irritability, lethargy, and hyporeflexia are common. Patients with severe infection may develop extensive hemorrhagic manifestations, shock, and seizures. The case-fatality ratio among untreated patients is 15% - 30%(Harrison et al., 1999).
              • Observed:
                AHF is a major public health problem in agricultural workers in the area of Argentina where it is endemic, with 100-800 recognized cases of AHF each year before the advent of immunization of high-risk individuals(Harrison et al., 1999),
            • Symptom -- Tremor of the hand or tongue :
              • Description: Tremor of the hand or tongue(Harrison et al., 1999).
              • Observed:
                5 of 31 cases(Harrison et al., 1999),
            • Symptom -- Gingival bleeding :
              • Description: Gingival bleeding(Harrison et al., 1999).
              • Observed:
                4 of 31 cases(Harrison et al., 1999),
            • Symptom -- Late neurological syndrome :
              • Description: Late neurological syndrome(Harrison et al., 1999).
              • Observed:
                4 of 31 cases(Harrison et al., 1999),
            • Symptom -- Conjunctival infection :
              • Description: Conjunctival infection(Harrison et al., 1999).
              • Observed:
                28 of 31 cases(Harrison et al., 1999),
            • Symptom -- Mouth enanthem :
              • Description: Mouth enanthem(Harrison et al., 1999).
              • Observed:
                27 of 31 cases(Harrison et al., 1999),
            • Symptom -- Cervical adenopathy :
              • Description: Cervical adenopathy(Harrison et al., 1999).
              • Observed:
                27 of 31 cases(Harrison et al., 1999),
            • Symptom -- Axillary petechiae :
              • Description: Axillary petechiae(Harrison et al., 1999).
              • Observed:
                18 of 31 cases(Harrison et al., 1999),
            • Symptom -- Exanthem :
              • Description: Exanthem(Harrison et al., 1999).
              • Observed:
                12 of 31 cases(Harrison et al., 1999),
            • Symptom -- Low back pain :
              • Description: Low back pain(Harrison et al., 1999).
              • Observed:
                20 of 31 cases(Harrison et al., 1999),
            • Symptom -- Myalgia :
              • Description: Myalgia(Harrison et al., 1999).
              • Observed:
                17 of 31 cases(Harrison et al., 1999),
            • Symptom -- Nausea :
              • Description: Nausea(Harrison et al., 1999).
              • Observed:
                14 of 31 cases(Harrison et al., 1999),
         4. Treatment Information:
            • Supportive therapy : Supportive therapy is important in the management of patients with arenal viral hemorrhagic fevers. Avoidance of travel and general trauma, gentle sedation and pain relief with conservative doses of opiates, the usual precautions for patients with bleeding diatheses (e.g., avoidance of intramuscular injections or acetylsalicylic acid), and careful maintenance of hydration are indicated. Bleeding should be managed by platelet transfusions and factor replacement, as indicated by clinical judgment and laboratory studies(Peters et al., 1996). Strict isolation and containment measures are not justified, because AHF is not usually contagious, although a few well-documented instances of interhuman transmission have been found. They can be prevented by avoiding intimate contacts with patients and by properly handling, decontaminating, and disposing of blood and secretions(Webb and Maiztegui, 1988).
              • Complication: Management of shock is difficult. Modest increases in hematocrit indicate a generalized vascular permeability problem, but not of the magnitude seen in diseases such as hantavirus pulmonary syndrome. Nevertheless, vigorous infusion of crystalloid carries a high risk of pulmonary edema. Cautious administrations of fluids and early use of pressors is indicated. Because of the implications of the low cardiac output seen in the Pichinde guinea pig model of arenaviral hemorrhagic fever and clinical experience with human disease, careful monitoring is important and Swan-Ganz catheterization is desirable(Peters et al., 1996).
            • Transfusion with immune plasma (Peters et al., 1996): Therapy of Junin virus infections with convalescent plasma has been studied carefully in humans and experimental animals and is quite efficacious, with reduction of mortality to 1% - 2% from 15% - 30% if initiated within the first 8 days of illness. The administration of convalescent plasma (usually 2 - 3 units, depending on the neutralizing titer) is the treatment of choice(Peters et al., 1996). A dose of no less than 3000 therapeutic units of neutralising antibodies per kg body weight is recommended(Enria et al., 1984).
              • Complication: A late neurologic syndrome (LNS) is observed 8 to 19% of AHF patients treated with immune plasma. It is characterized by a febrile syndrome, with cerebellar manifestations that are generally benign and self limited(Webb and Maiztegui, 1988).
              • Success Rate: Mortality is reduced to 1% - 2% from 15% -30%(Peters et al., 1996).
            • Ribavirin (Enria and Maiztegui, 1994): Ribavirin, a broad spectrum antiviral agent, is effective in the treatment of other viral hemorrhagic fevers, and the studies done with Junin virus infections to date indicate that this drug may also have a beneficial effect in Argentine hemorrhagic fever(Enria and Maiztegui, 1994).
              • Contraindicator: Although ribavirin should not be used when renal impairment is present, it may be necessary for severe disease in which the potential benefit may outweigh the risks. Rbavirin is contraindicated in pregnancy(Website 1).
              • Complication: Anemia (most commonly), insomnia, depression, irritability, and suicidal behavior have been reported with PO administration; with IV administration, reversible suppression of erythropoiesis, mild hemolysis, and mild direct hyperbilirubinemia are expected and generally manageable(Website 1).
   4. Prevention:
      1. Vaccine(Peters et al., 1996)
         • Description: A classical live-attenuated Junin vaccine referred to as Candid #1 has been developed and field tested in Argentina(Peters et al., 1996),
         • Efficacy:
           • Rate: In 1988-1990 a double-blind, placebo-controlled field trial was carried out in 6,500 volunteers; the vaccine reduced morbidity from serologically confirmed AHF from 22 cases in controls to a single case in vaccine recipients (p less than 0.001). Subsequently, 120,000 doses have been administered to high-risk residents of the endemic areas and only five mild cases of AHF have been reported in any vaccine recipient. The total annual number of cases in 1992-1994 has been less than 200; further observations will determine whether this is a result of vaccination of high-risk groups or of natural variations in disease incidence(Peters et al., 1996). The estimated effectiveness for the 1992-1999 period is 98.1%(Enria and Barrera Oro, 2002).
           • Duration:
         • Contraindicator: In spite of the counseling and pregnancy testing to avoid vaccination of pregnant women, 49 of 17,000 recipients have given birth within 9 months of vaccination. The occurrence of one case of anencephaly and one of meningomyelocoel in the offspring suggests that caution should be exercised in the use of Candid #1 in women of child-bearing age, but there has been no direct implication of the vaccine as being invasive or pathogenic for the fetus(Peters et al., 1996),
         • Complication: The vaccine has only minor reactogenicity in adults as measured in phase II and III studies, with no serious reactions observed in any recipient. Because of the need to extend coverage beyond the highest-risk groups of adult male residents of rural areas with high incidence of AHF, studies have begun to include children and women. To date no adverse reactions have been observed in 142 children as young as 4 years of age and seroconversion rates have been high(Peters et al., 1996),
   5. Model System:
      1. Rat
         1. Model Host: .
            Rat(Remesar et al., 1989),
         2. Model Pathogens: XJC13 Junin virus strain(Remesar et al., 1989).
         3. Description: A neurological model was used to evaluate protection conferred by the attenuated XJC13 Junin virus strain. Newborn rats inoculated intraperitoneally (ip) prove resistant, whereas 8-12 day-old animals infected by intracerebral route with the XJ prototype strain suffer 100% mortality with neurological signs. The aim of this study was to achieve protection in this model and attempt to elucidate the mechanisms involved in resistance(Remesar et al., 1989),
      1. Mouse
         1. Model Host: .
            Mouse, C3H/HeJ murine strain(Campetella et al., 1988),
         2. Model Pathogens: XJ Junin virus strain(Campetella et al., 1988).
         3. Description: The adult mouse model had been considered resistant to Junin virus (JV) infection. However, we found that C3H/HeJ murine strain proved highly susceptible up to 5 months of age to intracerebral inoculation with the prototype XJ JV strain, showing neurological signs and 80-90% mortality within 13 days(Campetella et al., 1988),
      1. Cebus apella
         1. Model Host: .
            Cebus apella(Caraballal et al., 1987, Oubina et al., 1986),
         2. Model Pathogens: (Caraballal et al., 1987, Oubina et al., 1986).
         3. Description: To assess the usefulness of the South American primate Cebus apella as a model for neurovirulence of Junin virus, eight monkeys were inoculated with 10(5) LD50 of the attenuated XJ-Clone 3 Junin virus strain by the intrathalamic route. The results obtained show that the XJ-Clone 3 strain can replicate in the primate CNS and to induce lesions and immunoglobulin deposition(Caraballal et al., 1987),
      1. Guinea pig
         1. Model Host: .
            Guinea pig(Kenyon et al., 1988),
         2. Model Pathogens: (Kenyon et al., 1988).
         3. Description: Guinea pigs infected with low-passage Junin virus of human origin showed viral strain dependent differences in mortality, LD50, time to death, and in viral spread and distribution. Different Junin strains appeared to cause at least two broad patterns of Argentine hemorrhagic fever in guinea pigs(Kenyon et al., 1988),
      1. Marmoset
         1. Model Host: .
            Marmoset, Callithrix jacchus(Avila et al., 1987),
         2. Model Pathogens: (Avila et al., 1987).
         3. Description: Argentine hemorrhagic fever (Junin virus) is a human viral disease for which immune therapy proves effective, though a late neurologic syndrome is occasionally associated with the treatment. We attempted to determine in the infected marmoset Callithrix jacchus whether immune therapy leads to protection and/or CNS damage. Immune serum treatment of Junin virus-infected marmosets was found to reduce mortality from 100% to 25%. Viremia and viral titers in organs were lowered, and late neurologic signs appeared in 30% of treated survivors(Avila et al., 1987),
2. Rodent
   1. Taxonomy Information:
      1. Species:
         1. Calomys spp. (Website 3):
            • Common Name: Calomys spp.
            • GenBank Taxonomy No.: 29105
            • Description: Junin virus, the etiological agent of Argentine hemorrhagic fever (AHF), has most commonly been isolated from the organs and body fluids of three species of rodents, Calomys musculinus, C. laucha, and Akodon azarae. In addition, the virus has been isolated from other rodent species such as Mus musculus and Oligoryzomys flavescens. The vesper mouse, Calomys musculinus, is considered the primary reservoir because it was the most commonly trapped rodent in the endemic area, and because persistent viremia and virus shedding via saliva was found both in naturally and laboratory-infected animals(Salazar-Bravo et al., 2002).
         2. Calomys musculinus (Website 4):
            • Common Name: Calomys musculinus
            • GenBank Taxonomy No.: 56212
            • Description: Junin virus, the etiological agent of Argentine hemorrhagic fever (AHF), has most commonly been isolated from the organs and body fluids of three species of rodents, Calomys musculinus, C. laucha, and Akodon azarae. In addition, the virus has been isolated from other rodent species such as Mus musculus and Oligoryzomys flavescens. The vesper mouse, Calomys musculinus, is considered the primary reservoir because it was the most commonly trapped rodent in the endemic area, and because persistent viremia and virus shedding via saliva was found both in naturally and laboratory-infected animals(Salazar-Bravo et al., 2002).
         3. Calomys laucha (Website 5):
            • Common Name: Calomys laucha
            • GenBank Taxonomy No.: 56211
            • Description: Junin virus, the etiological agent of Argentine hemorrhagic fever (AHF), has most commonly been isolated from the organs and body fluids of three species of rodents, Calomys musculinus, C. laucha, and Akodon azarae. In addition, the virus has been isolated from other rodent species such as Mus musculus and Oligoryzomys flavescens. The vesper mouse, Calomys musculinus, is considered the primary reservoir because it was the most commonly trapped rodent in the endemic area, and because persistent viremia and virus shedding via saliva was found both in naturally and laboratory-infected animals(Salazar-Bravo et al., 2002).
         4. Akodon azarae (Website 6):
            • Common Name: Akodon azarae
            • GenBank Taxonomy No.: 29095
            • Description: Junin virus, the etiological agent of Argentine hemorrhagic fever (AHF), has most commonly been isolated from the organs and body fluids of three species of rodents, Calomys musculinus, C. laucha, and Akodon azarae. In addition, the virus has been isolated from other rodent species such as Mus musculus and Oligoryzomys flavescens. The vesper mouse, Calomys musculinus, is considered the primary reservoir because it was the most commonly trapped rodent in the endemic area, and because persistent viremia and virus shedding via saliva was found both in naturally and laboratory-infected animals(Salazar-Bravo et al., 2002).
         5. Mus musculus (Website 7):
            • Common Name: Mus musculus
            • GenBank Taxonomy No.: 10090
            • Description: Junin virus, the etiological agent of Argentine hemorrhagic fever (AHF), has most commonly been isolated from the organs and body fluids of three species of rodents, Calomys musculinus, C. laucha, and Akodon azarae. In addition, the virus has been isolated from other rodent species such as Mus musculus and Oligoryzomys flavescens. The vesper mouse, Calomys musculinus, is considered the primary reservoir because it was the most commonly trapped rodent in the endemic area, and because persistent viremia and virus shedding via saliva was found both in naturally and laboratory-infected animals(Salazar-Bravo et al., 2002).

Not available for this pathogen.

NA

Ambrosio et al., 1986: Ambrosio AM, Enria DA, Maiztegui JI. Junin virus isolation from lympho-mononuclear cells of patients with Argentine hemorrhagic fever. Intervirology. 1986; 25(2); 97-102. [PubMed: 3013799].

Avila et al., 1987: Avila MM, Samoilovich SR, Laguens RP, Merani MS, Weissenbacher MC. Protection of Junin virus-infected marmosets by passive administration of immune serum: association with late neurologic signs. J Med Virol. 1987; 21(1); 67-74. [PubMed: 3025358].

Barrera Oro et al., 1990: Barrera Oro JG, McKee Jr KT, Spisso J, Mahlandt BG, Maiztegui JI. A refined complement-enhanced neutralization test for detecting antibodies to Junin virus. J Virol Methods. 1990; 29(1); 71-80. [PubMed: 2170437].

Buchmeier et al., 2001: Buchmeier MJ, Bowen MD, Peters CJ. Arenaviridae: The viruses and their replication. 1635-1668. In: . Field's Virology Fourth Edition Volume 2. 2001. Lippincott Williams and Wilkins, Philadelphia Pa.

Campetella et al., 1988: Campetella OE, Galassi NV, Sanjuan N, Barrios. Susceptible adult murine model for Junin virus. J Med Virol. 1988; 26(4); 443-451. [PubMed: 2850346].

Caraballal et al., 1987: Carballal G, Oubina JR, Molinas FC, Nagle C, de la Vega MT, Videla C, Elsner B. Intracerebral infection of Cebus apella with the XJ-Clone 3 strain of Junin virus. J Med Virol. 1987; 21(3); 257-268. [PubMed: 3031201].

Ellenberg et al., 2002: Ellenberg P, Edreira M, Lozano M, Scolaro. Synthesis and expression of viral antigens in Vero cells persistently infected with Junin virus. Arch Virol. 2002; 147(8); 1543-1557. [PubMed: 12181674].

Enria and Barrera Oro, 2002: Enria DA, Barrera Oro JG. Junin Virus Vaccines. 239-261. In: . Arenaviruses II. The Molecular Pathogenesis of Arenavirus Infections.. 2002. Springer-Verlag, Berlin Heidelberg.

Enria and Maiztegui, 1994: Enria DA, Maiztegui JI. Antiviral treatment of Argentine hemorrhagic fever. Antiviral Res. 1994; 23(1); 23-31. [PubMed: 8141590].

Enria et al., 1984: Enria DA, Briggiler AM, Fernandez NJ, Levis SC, Maiztegui JI. Importance of dose of neutralising antibodies in treatment of Argentine haemorrhagic fever with immune plasma. Lancet. 1984; 2(8397); 255-256. [PubMed: 6146809].

Franz et al., 1997: Franz DR, Jahrling PB, Friedlander AM, McClain DJ, Hoover DL, Bryne WR, Pavlin JA, Christopher GW, Eitzen EM Jr. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997; 278(5); 399-411. [PubMed: 9244332].

Garcia et al., 2000: Garcia JB, Morzunov SP, Levis S, Rowe J, Calderon G, Enria D, Sabattini M, Buchmeier MJ, Bowen MD, St Jeor SC. Genetic diversity of the Junin virus in Argentina: geographic and temporal patterns. Virology. 2000; 272(1); 127-136. [PubMed: 10873755].

Ghiringhelli et al., 1991: Ghiringhelli PD, Rivera-Pomar RV, Lozano ME, Grau O, Romanowski V. Molecular organization of Junin virus S RNA: complete nucleotide sequence, relationship with other members of the Arenaviridae and unusual secondary structures. J. Gen Virology. 1991; 72(9); 2129-2141. [PubMed: 1654373].

Harrison et al., 1999: Harrison LH, Halsey NA, McKee KT, Peters CJ, Barrera Oro JG, Briggiler AM, Feuillade MR, Maiztegui JI. Clinical case definitions for Argentine hemorrhagic fever. Clin Infect Dis. 1999; 28(5); 1091-1094. [PubMed: 10452640].

Jahrling, 1989: Jahrling PB. Arenaviruses and filoviruses. 857-891. In: . 6th Edition. Diagnostic procedures for viral, rickettsial, and chlamydial infections. 1989. American Public Health Association, Inc., Washington DC.

Kenyon et al., 1988: Kenyon RH, Green DE, Maiztegui JI, Peters. Viral strain dependent differences in experimental Argentine hemorrhagic fever (Junin virus) infection of guinea pigs. Intervirology. 1988; 29(3); 133-143. [PubMed: 2846464].

MMWR, 1988: Center for Disease Control and Prevention . Management of Patients with Suspected Viral Hemorrhagic Fever. Morb Mortal Weekly Report. 1988; 37(Supplemental 3); 1-16. [PubMed: 3126390].

Oubina et al., 1986: Oubina JR, Milei J, Bolomo NJ, Molindo A, Carballal G. Experimental Argentine hemorrhagic fever: myocardial involvement in Cebus monkey. J Med Primatol. 1986; 15(6); 391-397. [PubMed: 3025446].

Peters et al., 1996: Peters CJ, Buchmeier M, Rollin PE, Ksiazek TG. Arenaviruses. 1521-1551. In: . Field's Virology Third Edition Volume 1. 1996. , .

Peters, 2002: Peters CJ. Human infection with Arenaviruses in the Americas. 65-74. In: . Arenaviruses I. The epidemiology, molecular and cell biology of Arenaviruses. 2002. Springer-Verlag, Berlin Heidelberg.

Remesar et al., 1989: Remesar MC, Blejer JL, Lerman GD, Dejean C, Nejamkis MR. Protection against encephalitis in rats caused by a pathogenic strain of the Junin virus, using peripheral inoculation of an attenuated strain. Rev Argent Microbiol. 1989; 21(3-4); 120-126. [PubMed: 2562073].

Riera et al., 1997: Riera LM, Feuillade MR, Saavedra MC, Ambrosio. Evaluation of an enzyme immunosorbent assay for the diagnosis of Argentine haemorrhagic fever. Acta Virol. 1997; 41(6); 305-310. [PubMed: 9607087].

Salazar-Bravo et al., 2002: Salazar-Bravo J, Ruedas LA, Yates TL. Mammalian Reservoirs of Arenaviruses. 25-63. In: . Arenaviruses I. The epidemiology, molecular and cell biology of Arenaviruses. 2002. Springer-Verlag, Berlin Heidelberg.

Shepherd, 1988: Shepherd AJ. Viral hemorrhagic fevers: Laboratory diagnosis. 241-250. In: . Handbook of viral and rickettsial hemorrhagic fevers. 1988. CRC Press Inc, Boca Raton, Florida.

Southern, 1996: Southern PJ. Arenaviridae: The viruses and their replication. 1505-1519. In: . Field's Virology Third Edition Volume 1. 1996. Lippincott-Raven Publishers, Philadelphia PA.

Vitullo et al., 1987: Vitullo AD, Hodara VL, Merani MS. Effect of persistent infection with Junin virus on growth and reproduction of its natural reservoir, Calomys musculinus. Am J Trop Med Hyg. 1987; 37(3); 663-669. [PubMed: 2825553].

Webb and Maiztegui, 1988: Webb PA, Maiztegui JI. Argentine and Bolivian Hemorrhagic Fevers (South American Hemorrhagic Fevers). 145-154. In: . Handbook of viral and rickettsial hemorrhagic fevers. 1988. CRC Press Inc, Boca Raton, Florida.

Website 1: Viral Hemorrhagic Fevers

Website 10: Arenaviruses

Website 3: Calomys

Website 4: Calomys musculinus

Website 5: Calomys laucha

Website 6: Akodon azarae

Website 7: Mus musculus

Website 8: Viral Hemorrhagic Fevers

Website 9: Homo sapiens

 

PathInfo: Rebecca Wattam

HazARD: (for the section of Lab Animal Pathobiology & Management)

PHIDIAS: Yongqun "Oliver" He

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