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Abstract
Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.
Highlights
Arenaviruses are ambisense RNA viruses that are divided into Old World (OW) and New World (NW) virus groups based on their phylogenetic, serological, and geographical differences
Upon binding to the cellular receptor arenaviruses are internalized by vesicles, and are released into the cytoplasm through a pH-dependent membrane fusion step that is accomplished by the transmembrane portion of the viral glycoprotein glycoprotein subunit 2 (GP2) [58]
The fact that the DEDDH catalytic residues are conserved among all known arenaviruses and that its function to suppress IFNβ production has been demonstrated for both pathogenic (e.g., LASV and lymphocytic choriomeningitis virus (LCMV)) and non-pathogenic arenaviruses (e.g., Tacaribe virus (TCRV) and MOPV) suggests that this is a general mechanism of innate immune suppression by these viruses, allowing them to replicate in either their natural hosts or in infected humans
Summary
Arenaviruses are ambisense RNA viruses that are divided into Old World (OW) and New World (NW) virus groups based on their phylogenetic, serological, and geographical differences. While the prototypic OW arenavirus LCMV with worldwide distribution causes only mild illness in immunocompetent individuals, two other known OW arenaviruses (LASV and LUJV, both found in Africa) can cause severe hemorrhagic fever (HF) in humans. Several of the NW arenaviruses in South America (e.g., JUNV, MACV, SABV, GTOV, and CHPV) can cause severe hemorrhagic fevers (HF). There are currently limited preventative and therapeutic options for patients infected with these highly pathogenic viruses. We will summarize current understanding of the roles of the different viral and cellular factors that contribute to the degrees of arenavirus virulence in humans
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