Isolation and Antigenic Characterization of Lassa Virus

Buckley, Sonja M.; Casals, Jordi; Downs, W. G.

doi:10.1038/227174a0

Cited by 68 publications

(30 citation statements)

References 3 publications

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“…Lassa fever is a viral haemorrhagic fever caused by an arenavirus, first described in West Africa in the 1950s, although the virus was not isolated until 1969 [1,2]. Arenaviruses produce mostly silent, persistent infection in rodents, and their origin is thought to date back to the evolution of different rodent species, perhaps as much as 9 million years ago [3].…”

Section: The Public Health Problem Of Lassa Fevermentioning

confidence: 99%

Towards a human Lassa fever vaccine

Fisher‐Hoch

McCormick

2001

Reviews in Medical Virology

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Arenaviruses, such as Lassa fever, establish chronic infections in rodents, leading to incidental transmission to humans. Lassa fever is a clinically severe disease, yet the absence of second attacks implies life-long immunity. The aim of this review is to consider whether such immunity could be provided by vaccines. The South American arenaviruses are controlled by neutralising antibody and a clinical trial of live, attenuated vaccine for Argentinian haemorrhagic fever provided 84% protection. In contrast, there is no evidence for protective humoral immunity against Old World arenaviruses which are controlled by cell-mediated immune responses. Nevertheless, vaccination with Lassa glycoproteins can protect monkeys from disease, implying that protection may be achievable, even though the immunological mechanisms are distinct. Recombinant vaccinia viruses expressing various forms of Lassa glycoproteins can protect both guinea-pigs and primates, while additional protective responses can be mounted against nucleocapsid genes. However, vaccines based upon vaccinia constructs are no longer tenable for African populations with a high seroprevalence of HIV infection. The scientific challenge now remains to find alternative methods of delivering T-cell immunity against glycoproteins from Lassa virus in ways which can overcome the local economic and political hurdles to vaccine development.

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Section: The Public Health Problem Of Lassa Fevermentioning

confidence: 99%

Towards a human Lassa fever vaccine

Fisher‐Hoch

McCormick

2001

Reviews in Medical Virology

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“…LCMV is the prototypic member of the family Arenaviridae, which includes important human pathogens such as Lassa fever and Machupo, Sabia, and Junin viruses (Buckley et al 1970;Peters et al 1996;Southern et al, 1987). Its genome consists of two negative-strand RNA segments, large (L) and short (S) fragments (Riviere et al 1985;Singh et al 1987;Southern 1996).…”

Section: Lcmv and Immunosuppressive Variantsmentioning

confidence: 99%

Infection of Dendritic Cells by Lymphocytic Choriomeningitis Virus

Sevilla

Kunz

McGavern

et al. 2003

Current Topics in Microbiology and Immunology

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Dendritic cells (DCs) comprise the major antigen-presenting cells (APCs) of the host, uniquely programmed to stimulate immunologically naïve T lymphocytes. Viruses that can target and disorder the function of these cells enjoy a selective advantage. The cellular receptor for lymphocytic choriomeningitis virus (LCMV), Lassa fever virus (LFV), and several other arenaviruses is α-dystroglycan (α-DG). Among cells of the immune system, CD11c + and DEC-205 + DCs primarily and preferentially express α-DG. By selection, strains and variants of LCMV generated as quasi-species that bind α-DG with high affinity replicate in the majority of CD11c + and DEC-205 + (>75%) DCs, causing a generalized immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to α-DG display minimal replication in CD11c + and DEC-205 + DCs (<10%), rarely replicate in the white pulp, and generate a robust anti-LCMV CTL response that clears the virus infection. Hence, receptor-virus interaction on DCs in vivo is an essential step in the initiation of virus-induced immunosuppression and viral persistence. Investigation into the mechanism of how virus-infected DCs cause immunosuppression reveals loss of MHC class II surface expression and costimulatory molecules on surface of such DCs. As a consequence DCs are unable to act as APCs, initiate immune responses, and have a defect in migration into the T cell area. These data indicate that LCMV infection influences DC maturation and migration, leading to decreased T cell stimulatory capacity of DCs, events essential for the initiation of immune responses. Because several other viruses known to cause immunosuppression (HIV, measles) interact with DCs, the observations noted here are likely a common selective mechanism by which viruses also are able to evade the host s immune system.

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“…is the prototypic member of the family Arenaviridae, which includes important human pathogens such as Lassa fever and Junin viruses (11,41,43,53,55). In addition, LCMV provides one of the most widely used model systems to study viral persistence and pathogenesis (7,10,37,38,39,40,45).…”

Section: Lymphocytic Choriomeningitis Virus (Lcmv)mentioning

confidence: 99%

RING Finger Z Protein of Lymphocytic Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA Replication of an LCMV S-Segment Minigenome

Cornu

Torre

2001

J Virol

134

120

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Arenaviruses have a bisegmented negative-strand RNA genome whose proteomic capability is limited to only four polypeptides, namely, nucleoprotein (NP), surface glycoprotein (GP) that is proteolytically processed into GP1؉GP2, polymerase (L), and a small (11-kDa) RING finger protein (Z). The role of Z during the Lymphocytic choriomeningitis virus (LCMV) life cycle is poorly understood. We investigated the function of Z in virus transcription and replication by using a reverse genetic system for the prototypic arenavirus LCMV. This system involves an LCMV minigenome and the minimal viral trans-acting factors (NP and L), expressed from separated cotransfected plasmids. Cotransfection of the Z cDNA strongly inhibited LCMV minigenome expression. The effect required synthesis of Z protein; its magnitude was dose dependent and occurred with levels of Z protein substantially lower than those observed in LCMV-infected cells. Coexpression of Z did not prevent the encapsidation of plasmid supplied minigenome, but it affected both transcription and RNA replication similarly. Mutations in Z that unfolded its RING finger domain eliminated its inhibitory activity, but RING proteins not related to Z did not affect LCMV minigenome expression. Consistent with the minigenome results, cells transiently expressing Z exhibited decreased susceptibility to infection with LCMV. Lymphocytic choriomeningitis virus (LCMV)is the prototypic member of the family Arenaviridae, which includes important human pathogens such as Lassa fever and Junin viruses (11,41,43,53,55). In addition, LCMV provides one of the most widely used model systems to study viral persistence and pathogenesis (7,10,37,38,39,40,45).The LCMV genome consists of two negative-sense singlestranded RNA segments, L and S, with approximate sizes of 7.2 and 3.4 kb, respectively (44,48,52,53). Each RNA segment has an ambisense coding strategy, encoding two proteins in opposite orientations, separated by an intergenic region (IGR) (48, 53). The S RNA directs synthesis of the three major structural proteins: the nucleoprotein, NP (ca. 63 kDa) (44,48,53), and the two virion glycoproteins, GP-1 (40 to 46 kDa) and GP-2 (35 kDa), which are derived by posttranslational cleavage of a precursor polypeptide, GP-C (75 kDa) (48,53,54,60). Tetramers of GP-1 and GP-2 make up the spikes on the virion envelope and mediate virus interaction with host cell surface receptor (6, 13). The L RNA segment encodes a high-molecular-mass protein (L, ca. 200 kDa) (52), which has the characteristic motifs conserved in all of the viral RNA-dependent RNA polymerases (46), and a small (11-kDa) RING finger protein (Z) (50). The NP, the most abundant viral protein in virus-infected cells, is associated with the viral RNA to form the nucleocapsid (NC), which is the template for the viral RNA polymerase (23,24). The L protein is thought to be the main viral component of the arenavirus polymerase (23,48,53). The NC associated with the viral polymerase constitutes the viral ribonucleoprotein (RNP), which is active in ...

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Isolation and Antigenic Characterization of Lassa Virus

Cited by 68 publications

References 3 publications

Towards a human Lassa fever vaccine

Towards a human Lassa fever vaccine

Infection of Dendritic Cells by Lymphocytic Choriomeningitis Virus

RING Finger Z Protein of Lymphocytic Choriomeningitis Virus (LCMV) Inhibits Transcription and RNA Replication of an LCMV S-Segment Minigenome

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