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.

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 (BST2)	filoviridae, influenza virus, hiv-1 lasv vsv	budding	prevent release of new virions
PKR (EIF2AK2)	all viruses	translation	targets eif2a
IFIT1 IFIT2 IFIT3	Influenza, HPV, MHV, RVSV, SINV, VSV, WNV	mRNA translation	IFIT1 binds mRNAs without2'-O methylation
IFIT5
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	The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry Samad Amini-Bavil-Olyaee, Youn Jung Choi, Jun Han Lee, Mude Shi, I-Chueh Huang, Michael Farzan, Jae U Jung Cell Host Microbe April 17, 2013; 13: 452?464
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 (MxA)	CVB, Influenza, HCV, HPIV3, LACV, MV, SFV, THOV, VSV	primary transcription? nucleocapsid shutling?	formation of highly ordered oligomers?
MX2 (MxB)	HIV-1, HNTV, LACV, RVFV, VSV
OAS1 OAS2 OAS3	CHIKV, DENV, EMCV, HCV, SFV, SINV, WNV	replication/translation	activate RNaseL to degrade viral RNA
PML (TRIM19)		replication/transcription	organize multiprotein nuclear bodies
SP100		replication/transcription	component of multiprotein nuclear bodies
Viperin (RSAD2)	DENV, Influenza, HCMV, HCV, SINV, WNV	budding	changes membrane composition
TRIM5	retroviridae
ZAP (ZC3HAV1)	Ebov, influenza, MBGV, NDV, retrovirus , SINV	transcription/translation	mRNA degradation
OASL	HCV	replication