Arm race between Rift Valley fever virus and host

Abstract

Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV), an emerging arbovirus within the Phenuiviridae family of Bunyavirales that has potential to cause severe diseases in both humans and livestock. It increases the incidence of abortion or foetal malformation in ruminants and leads to clinical manifestations like encephalitis or haemorrhagic fever in humans. Upon virus invasion, the innate immune system from the cell or the organism is activated to produce interferon (IFN) and prevent virus proliferation. Meanwhile, RVFV initiates countermeasures to limit antiviral responses at transcriptional and protein levels. RVFV nonstructural proteins (NSs) are the key virulent factors that not only perform immune evasion but also impact the cell replication cycle and has cytopathic effects. In this review, we summarize the innate immunity host cells employ depending on IFN signal transduction pathways, as well as the immune evasion mechanisms developed by RVFV primarily with the inhibitory activity of NSs protein. Clarifying the arms race between host innate immunity and RVFV immune evasion provides new avenues for drug target screening and offers possible solutions to current and future epidemics.

Mechanism of Immune Evasion in Mosquito-Borne Diseases

“…While most human infections are mild or asymptomatic, in rare cases, RVFV can cause severe disease, including hemorrhagic fever and encephalitis [ 271 ]. The entry of the RNA virus into the host is followed by a complex set of innate immune responses [ 272 ]. Retinoic acid-inducible gene I (RIG-I), melanoma differentiation factor 5 (MDA5), and Toll-like receptors (TLRs) are among the pattern recognition receptors (PRR) that recognize this virus [ 273 ].…”

“…Retinoic acid-inducible gene I (RIG-I), melanoma differentiation factor 5 (MDA5), and Toll-like receptors (TLRs) are among the pattern recognition receptors (PRR) that recognize this virus [ 273 ]. RIG-I also triggers an interferon response inside the host cell and maintains an antiviral state [ 272 ]. The RVFV has developed sophisticated strategies to evade the immune system and dysregulate the immunological pathways to successfully initiate infection and manifest into a clinical condition, which will be discussed briefly.…”

“…This spliced isoform RIOK-3 X2 lowers the expression of interferon and helps in the successful evasion of the host’s immune pathways [ 277 ]. RIOK-3 X2 also plays a role in increasing the inflammatory NF-κβ response [ 272 ].…”

“…Eukaryotic transcription factor IIH helps in the initiation of transcription by eukaryotic RNA polymerase II. The core complex of TF IIH comprises XPD, XPB, p44, p62, p8, p34, and p52 [ 272 ]. RVFV NSs can competitively bind to p44 and prevent it from binding with XPD [ 281 ].…”

“…RVFV-infected cells have shown nuclear deformities such as micronuclei and lobulated nuclei mainly due to defects in chromosomal cohesion and segregation [ 284 ]. These damages occur due to the accumulation of NSs filaments inside the nucleus [ 272 ]. The filaments also play a key role in arresting the cell cycle at the S or G0/G1 phases [ 285 ].…”