Human Type I Interferon Antiviral Effects in Respiratory and Reemerging Viral Infections

Table 1

Role of IFN-I in respiratory virus and flavivirus infections.

Virus	Model	Effect	Main finding	References
Human respiratory viruses
Influenza virus	Human (in vivo)	Protective	Hospitalized subjects show enrichment for a minor IFITM3 allele that leads to reduced influenza virus restriction	[70]
	Human (in vivo)	Pathogenic	High levels of IFN-α2 at enrollment predicted progression to severe disease	[278]
RSV	Human (in vitro)	Protective	Age and premature birth were independently associated with attenuated RIG-I-dependent IFN-α responses	[89]
	Human (in vivo)	Protective	Infants with severe RSV bronchiolitis have lower type-I IFN levels	[90]
hMPV	Mouse (in vivo)	Pathogenic	IFN-I contributed to disease pathogenesis due to increased inflammatory lung disease during infection	[102]
PIV	Human (in vivo)	Protective	Mean quantities of the virus in the secretions of those children with interferon was significantly lower compared to those without detectable IFN	[65, 117]
HRV	Human (in vitro); Human (in vivo)	Protective	Exogenous IFN-α, IFN-β significantly reduce HRV replication	[130, 131]
HCoV	Human (in vivo)	Pathogenic	High levels of IFN correlated with early sequelae	[148]
	Human (in vivo)	Protective	Patients treated with IFN show clinical response	[289, 290]
Emerging flaviviruses
DENV	Human (in vivo)	Protective	Higher levels of IFN-α are observed in patients with milder dengue disease	[77, 190, 193–196]
	Human (in vivo)	Pathogenic	Higher levels of IFN-β in severe vs. nonsevere dengue children	[197]
	Human (in vivo)	Pathogenic	Higher levels of IFN-β in primary DHF patients compared to those with primary DF	[198]
ZIKV	Human (in vivo)	Protective	SNP at TLR-3 that decreased IFN-I response has been associated with microcephaly in newborns	[232]
	Human (in vitro)	Protective	Replication of Asian ZIKV strain Brazil 2015 (associated with neurodevelopmental disorders) was less sensitive to IFN-I, compared to other ZIKV strains	[233]
WNV	Human (in vitro)	Protective	PI3K that induces IFN-I controls WNV infection	[238]
	Human (in vitro)	Protective	Early activation of RLR or IFN-I signaling could block WNV infection	[239]
	Human (in vivo)	Inconclusive	IFN-α treatment was well tolerated and might have potential beneficial effects, due to treatment or chance	[293–296]
YFV	Human (in vitro)	Protective/pathogenic	ISGs shown to inhibit or enhance viral replication	[258]
JEV	Human (in vitro)	Protective	IFN-α at higher concentrations showed more efficacy in combating the replication of JEV	[297]
	Human (in vivo)	Inconclusive	No benefits from IFN-α2a treatment against children with JEV infection	[298]
SLEV	Human (in vivo)	Protective	IFN-α2b therapy for meningoencephalitis suggested a beneficial effect on the early neurologic course of the disease and clinical improvement	[299, 300]