Abstract
The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.
Highlights
Arenaviruses are enveloped, negative-sense, single-stranded RNA viruses [1]
Replicate slightly more efficiently in wild-type cells than in protein kinase R (PKR)-deficient cells. These results suggest that pathogenic New World (NW) arenaviruses exploit PKR activation to facilitate virus infection by attenuating
One possibility is that the IFN antagonist activities of the NPs of pathogenic NW arenaviruses (JUNV and Machupo viruses (MACV)) are weaker than that of Lassa virus (LASV) NP during virus infection, explaining why the retinoic acid-inducible gene I (RIG-I)/interferon regulatory factors 3 (IRF3) signaling pathway is active in JUNV and MACV but not in
Summary
Arenaviruses are enveloped, negative-sense, single-stranded RNA (ssRNA) viruses [1]. The family. Clade A contains the prototypic Pichinde virus that, while non-pathogenic to humans, causes hemorrhagic disease in rodents that is similar to Lassa fever (LF) in humans [16,17]. Nosocomial transmission of LASV, JUNV, and MACV has been reported [1,21,22] Within endemic areas, both OW and NW arenaviruses are responsible for significant human disease. Among the highly pathogenic arenaviruses, LASV is the most prevalent and clinically important, with an estimated 100,000–300,000 infections and 5000 deaths in West Africa each year [23]. The exact mechanisms behind the development of long-term sequelae after infection by highly pathogenic arenaviruses remain to be determined, but cell-mediated immunity may be involved. The World Health Organization has listed LF in the Blueprint list of priority diseases for which there is an urgent need for accelerated research and development
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