Lassa Virus Infection of Rhesus Monkeys: Pathogenesis and Treatment with Ribavirin

Jahrling, Peter B.; Hesse, Richard; Eddy, Gerald A.; Johnson, Karl M.; Callis, R. T.; Stephen, Edward L.

doi:10.1093/infdis/141.5.580

Cited by 213 publications

(157 citation statements)

References 8 publications

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“…The WE strain of LCMV is hepatotropic in mice, guinea pigs and primates (Riviere et al 1985, Zinkernagel et al 1986, Lukashevich et al 2002, but in contrast to murine LCMV infections, LCMV-WE infection of rhesus macaques can resemble Lassa hemorrhagic fever in human beings (Jahrling et al 1980, Peters et al 1987, Lukashevich et al 2002. The Armstrong (ARM) strain of LCMV does not cause overt disease in monkeys, even after intravenous inoculation (Danes et al 1963, Peters et al 1987, Lukashevich et al 2002.…”

mentioning

confidence: 99%

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Rodas

Cairo

Djavani

et al. 2009

Mem. Inst. Oswaldo Cruz

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Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs). Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK) and γδ T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3 -CD8 + or CD3 -CD16 + and not the NKT (primarily CD3 + CD56 + ) subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and γδ T cells, indicating that this is not a pathogenic event. Vγ9 T cells, representing the majority of circulating γδ T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections. Keywords: NK cells -γδ T -rhesus macaque -LCMV -hemorrhagic feverArenaviruses are rodent-borne pathogens that have occasionally been known to cause lethal diseases in human beings (Oldstone 2002, Salvato & Rodas 2005. Every year, Lassa fever and the South American hemorrhagic fever viruses account for almost half a million cases worldwide, with approximately 16% mortality (Jahrling et al. 1985, McCormick et al. 1986, Fisher-Hoch et al. 2000. Although rodents serve as a reservoir for arenaviruses, studies of hemorrhagic fever have relied on guinea pig, hamster and primate models rather than mouse models because the disease mechanism is fundamentally different in non-reservoir species (Peters et al. 1987).Numerous murine studies of viral persistence and cell-mediated immunity have involved the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV) , Ahmed et al. 1984, Salvato et al. 1991. The WE strain of LCMV is hepatotropic in mice, guinea pigs and primates (Riviere et al. 1985, Zinkernagel et al. 1986, Lukashevich et al. 2002, but in contrast to murine LCMV infections, LCMV-WE infection of rhesus macaques can resemble Lassa hemorrhagic fever in human beings (Jahrling et al. 1980, Peters et al. 1987, Lukashevich et al. 2002. The Armstrong (ARM) strain of LCMV does not cause overt disease in monkeys, even after intravenous inoculation (Danes et al. 1963, Peters et al. 1987, Lukashevich et al. 2002.Several immunological studies have shown the importance of CD8 T lymphocytes in both protection and in induction of immuno-pathogenesis i...

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confidence: 99%

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Rodas

Cairo

Djavani

et al. 2009

Mem. Inst. Oswaldo Cruz

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“…For prepared virus, and blood and organ homogenates of LCMV-inoculated animals. LCMV infectivity was measured in p.f.u, in a Vero cell monolayer-agarose overlay system (Jahrling & Eddy, 1980;Genovesi & Peters, 1987 a, b). Infective LCMV titres are expressed as mean log10 p.f.u.…”

Section: Methodsmentioning

confidence: 99%

“…Tissues were examined for LCMV antigens by direct immunofluorescence (Jahrling & Eddy, 1980). Organs, frozen in a polyethylene glycol compound at -70 °C, were cut using a cryostat into tissue sections and acetonefixed onto glass slides.…”

Section: Methodsmentioning

confidence: 99%

“…Sera were heated at 56 °C for 30 rain and tested for LCMV antibody by an indirect immunofluorescent antibody test (IFAT) and in an in vitro assay for neutralizing antibody, using a constant-serum varied-virus format (Jahrling & Eddy, 1980;Peters et al, 1987). Details of both procedures were previously reported (Genovesi & Peters, 1987a, b).…”

Section: Methodsmentioning

confidence: 99%

“…Bar marker represents 100 Ixm. (Walker et al, 1975a(Walker et al, , b, 1982Murphy et al, 1976;Buchmeier & Rawls, 1977;Jahrling et al, 1980Jahrling et al, , 1981Jahrling et al, , 1982Peters, 1984;Kenyon et al, 1985;Riviere et al, 1985;Peters et al, 1987).…”

Section: Body Weightmentioning

confidence: 99%

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Susceptibility and Resistance of Inbred Strains of Syrian Golden Hamsters (Mesocricetus auratus) to Wasting Disease Caused by Lymphocytic Choriomeningitis Virus: Pathogenesis of Lethal and Non-lethal Infections

Genovesi¹,

Johnson

Peters³

1988

Journal of General Virology

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SUMMARYIn different strains of inbred Syrian golden hamsters (Mesocricetus auratus), the lymphocytic choriomeningitis virus (LCMV) strains WE and Armstrong (ARM) produced systemic infection with infective virus and viral antigens detected predominantly in reticuloendothelial organs. Host and virus strain-dependent fatal wasting disease also occurred. After infection with WE, all MHA and PD4 hamsters died of a progressive wasting disease and infectivity persisted in organs at relatively high titres. LSH and CB strain hamsters resisted lethal disease and totally eliminated infection. LVG and LHC strain hamsters were intermediate in susceptibility to WE; some died of wasting and had persistently infected organs, while others cleared infection and survived. ARM was avirulent causing an inapparent infection in all hamsters. LCMV antibody responses were temporally comparable for all hamsters with either lethal or non-lethal infection. Histologically, lymphoid hyperplasia and low-grade systemic perivascular mononuclear leukocyte infiltration were found in all LCMV-infected hamsters. However, non-necrotic segmental ileal changes, which included vascular congestion, minimal haemorrhage and crypt epithelial growth extension into the intestinal wall, were found in susceptible hamsters when infected with the lethal WE strain.

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Hemorrhagic Fever Viruses as Biological Weapons

Borio

Inglesby

Peters

et al. 2002

JAMA

627

467

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Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

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Lassa Virus Infection of Rhesus Monkeys: Pathogenesis and Treatment with Ribavirin

Cited by 213 publications

References 8 publications

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Susceptibility and Resistance of Inbred Strains of Syrian Golden Hamsters (Mesocricetus auratus) to Wasting Disease Caused by Lymphocytic Choriomeningitis Virus: Pathogenesis of Lethal and Non-lethal Infections

Hemorrhagic Fever Viruses as Biological Weapons

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