Viral Infection: An Evolving Insight into the Signal Transduction Pathways Responsible for the Innate Immune Response

Table 1

Examples of parallel evolution of viral innate immune evasion mechanisms.

(a) Bacteria

Mechanism	Viral evasion strategy	Virus protein
CRISPER	Genetic variation of DNA	DNA polymerase [26]
Psp-induced signaling	Unknown (Psp genetic variation)	Unknown
Restriction/methylation	Methylation of viral target DNA	Acquired bacterial methylase [26]
Apoptosis	Lysogeny/tolerance	Phage lysis gene regulation [27]

(b) Drosophila

Mechanism	Evasion strategy	Viral protein
DICER1	Genetic variation of DNA	Virus encodes miRNAs [28]
Vago	IkB, Jak/Stat inhibitors	Viral IkB, unknown inhibitor of Jak/STAT [29]
DICER2	Binding of ds RNA	FHV-B2 protein [30]
Apoptosis	Inhibitor of apoptosis (IAP)	Baculovirus p35 [31, 32]

(c) Mammalian systems

Mechanism	Evasion strategy	Viral protein
Interferon signaling	dsRNA binding	Influenza virus NS1 [33], VACV E3 (also inhibits DNApol III DNA sensing) [34]
	Inhibition of signaling	VACV N1 family [5, 35–37], HCV NS3A/4 [38], influenza virus NS1 [33], HCV core proteins inhibit Jak/Stat signaling [39], HCV NS5A inhibits MyD88 [40],; HIV Vif, and Vpr degrade IRF3 [37]
	Inhibition of IFN binding	VACV soluble IFN alpha/beta receptors [41]
Viral RNA/DNA sensing	Inhibitors of RIG-I	HCV NS3A/4 proteolytic cleavage of MAVS [38, 42]
	Inhibitors of MDA5, LGP2	Paramyxovirus V proteins [43]
	Inhibitors of DDX3	VACV K7 [5]
	Inhibitors of the AIM2/NLRP3 Inflammasome	KSHV vNLR [44], myxoma virus M013 [45]
	Inhibitors of proteins activated downstream of the AIM2/NLRP3 inflammasome	Cowpox virus crmA; VACV SPI-2, sIL-1𝛽R, and sIL-18R [41]
	DAI	EBV EBERmiRNAs [25]
Programmed cell death	Viral inhibitor of apoptosis (IAP)	KSHV vFLIP [46]
	Viral bcl-2s	EBV bhrf1 and balf1 [47, 48],
		KSHV orf16 [49]
	Blockade of IL-1-mediated pyroptosis	Poxvirus crmA, sIL-1𝛽, sIL18 [41]