Abstract
Endemic to West Africa and South America, mammalian arenaviruses can cross the species barrier from their natural rodent hosts to humans, resulting in illnesses ranging from mild flu-like syndromes to severe and fatal haemorrhagic zoonoses. The increased frequency of outbreaks and associated high fatality rates of the most prevalent arenavirus, Lassa, in West African countries, highlights the significant risk to public health and to the socio-economic development of affected countries. The devastating impact of these viruses is further exacerbated by the lack of approved vaccines and effective treatments. Differential immune responses to arenavirus infections that can lead to either clearance or rapid, widespread and uncontrolled viral dissemination are modulated by the arenavirus multifunctional proteins, NP and Z. These two proteins control the antiviral response to infection by targeting multiple cellular pathways; and thus, represent attractive targets for antiviral development to counteract infection. The interplay between the host immune responses and viral replication is a key determinant of virus pathogenicity and disease outcome. In this review, we examine the current understanding of host immune defenses against arenavirus infections and summarise the host protein interactions of NP and Z and the mechanisms that govern immune evasion strategies.
Highlights
RNA viruses, despite the limited size of their genomes, pose serious challenges to global public health [1,2,3]
We examine the current understanding of host immune defenses against arenavirus infections and summarise the host protein interactions of NP and Z and the mechanisms that govern immune evasion strategies
Biochemical, mutagenesis and structural studies have shown that NP is comprised of an N-terminal RNA-binding domain that mediates viral ribonucleoprotein (vRNP) assembly, linked via a flexible C-terminal 30 –50 exoribonuclease (DEDDh family) domain which is highly conserved across the arenavirus family (Figure 4) [96,98,99,100]
Summary
RNA viruses, despite the limited size of their genomes, pose serious challenges to global public health [1,2,3]. These limited treatment options highlight the urgent need for continued research into developing antiviral therapeutics to target arenavirus infection This is further exacerbated by the lack of approved vaccines against arenavirus VHFs. The live-attenuated Candid#1 strain of JUNV has shown high efficacy against Argentine haemorrhagic fever caused by the etiological agent, JUNV [34,46]. The live-attenuated Candid#1 strain of JUNV has shown high efficacy against Argentine haemorrhagic fever caused by the etiological agent, JUNV [34,46] This vaccine, is not licensed outside of Argentina and has been shown to be ineffective against other arenavirus infections, including MACV and LASV. LASV [47,48,49]
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