Antiviral state inhibition

Cellular antiviral state

Once a virus enters host cell, different type of sensors recognize the intruder and active a signaling cascade leading to the expression of several hundreds of genes leading to the establishment of the antiviral state briefly described below.

isg15 tetherin pml pkr apobec

Cellular antiviral state inhibition

A lot of viruses encode proteins to counteract the antiviral state to be able to efficiently perform their replication cycle (including genome replication and budding). For example, the host PML protein is targeted by many DNA viruses that need to subvert the host nucleus to replicate their own genomic DNA. Other viruses target host tetherin whose function is to prevent budding of viruses and thus their spread.

Table describing most studied Interferon stimulated genes:

Antiviral state effectors
Host protein targeted viruses viral life cycle antiviral activity Reference
ADAR HCV, HDV replication viral RNA editing
APOBEC3G retroviridae replication cytidine deamination of viralgenome
MICA , MICB All viruses NA Host cell killing by NK
Tetherin filoviridae, influenza virus, hiv-1 lasv vsv budding prevent release of new virions
PKR all viruses translation targets eif2a
IFIT1 IFIT2 IFIT3 Influenza, HPV, MHV, RVSV, SINV, VSV, WNV mRNA translation IFIT1 binds mRNAs without2’-O methylation
IFITM1 HCV entry tight junction endocytosis
IFITM2 DENV, EBOV, Influenza, HIV-1, SARS-CoV, VSV, WNV, YFV entry may target endocytic pathways
IFITM3 DENV, EBOV, Influenza, HIV-1, SARS-CoV, VSV, WNV, YFV entry/exit Disrupt cholesterol homeostasis
ISG15 Influenza, HIV-1, HSV-1, JEV, MHV-68, SINV replication, assembly, exit inhibits proteins function nby ISGylation
ISG20 BVDV, DENV, EMCV, Influenza, HCV, SINV, VSV, WNV, YFV viral RNA synthesis exonuclease
MX1 CVB, Influenza, HCV, HPIV3, LACV, MV, SFV, THOV, VSV primary transcription? nucleocapsid shutling? formation of highly ordered oligomers?
OAS1 OAS2 OAS3 CHIKV, DENV, EMCV, HCV, SFV, SINV, WNV replication/translation activate RNaseL to degrade viral RNA
PML replication/transcription organize multiprotein nuclear bodies
SP100 replication/transcription component of multiprotein nuclear bodies
Viperin DENV, Influenza, HCMV, HCV, SINV, WNV budding changes membrane composition
TRIM5 retroviridae
ZAP Ebov, influenza, MBGV, NDV, retrovirus , SINV transcription/translation mRNA degradation
OASL HCV replication

MICA or MICB activates NK cell to induce lysis of host cell. These genes are regulated by miRNA, and herpesviruses inhibit its function by similar miRNAs.