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. 2017 Dec 6;8:1707. doi: 10.3389/fimmu.2017.01707

Table 1.

Interferon lambda (IFNλ) and IFNα/β functions in viral infection.

Virus infection Role of IFNλ Role of IFNα/β
Negative-sense RNA viruses
Human metapneumovirus (−ssRNA Pneumoviridae)

  • IFNλ treatment reduces titer in murine model (57)

  • Increased titers in mice lacking IFNλR and IFNAR (49)

  • Increased titers in mice lacking IFNλR and IFNAR (49)

  • Increased titers and reduced CD8 T cell response in mice lacking IFNAR (58)
Influenza virus (−ssRNA Orthomyxoviridae)

  • Increased virus titers in human cells and murine models in the absence of IFNλR (48, 49)

  • IFNλ reduced influenza A virus (IAV) titers with minimal-associated pulmonary damage in murine in vivo models (35, 48, 54, 55)

  • Increased IFNλ [human single nucleotide polymorphism (SNP) rs8099917] correlates with increased Th1 skewing of CD4 T cell response and reduced sero-conversion following vaccination (15)

  • Mice lacking IFNAR1 and IFNλR in the stromal compartment are more susceptible to IAV infection (52)

  • Therapeutic treatment of IAV-infected mice with IFNα leads to reduced IAV titers, but pulmonary damage (54)
Lymphocytic choriomeningitis virus (−ssRNA Arenaviridae)

  • IFNλ2 and IFNλ3 inhibit infection of human lung epithelial cells (59)

  • IFNλR−/− mice have no change in virus titer, but increased CD8 T cell response to acute infection and reduced CD8 T cell response to chronic infection (60, 61)

  • Blockade of type I IFN controls persistent infection (62, 63)
Respiratory syncytial virus (−ssRNA Paramyxoviridae)

  • Increased titers in mice lacking IFNλR and IFNAR (49)

  • Increased titers in mice lacking IFNλR and IFNAR (49)
Positive-sense RNA viruses
Dengue (+ssRNA Flaviviridae)

  • IFNλ1 induces expression of CCR7 and in vitro dendritic cell (DC) migration (64)

  • IFNλ1 and IFNλ2 inhibit virus in a human epithelial cell line (65)

  • Mice lacking IFNAR are more susceptible to infection (66)

  • Mice lacking IFNAR on CD11c+ or LysM+ cells have increased disease during infection, but still mount protective CD8 T cell responses against the virus (67)
Hepatitis C virus (HCV) (+ssRNA Flaviviridae)

  • SNPs rs4803217, rs8099917, rs12979860, and rs368234815 correlate with response to IFN therapeutic and spontaneous virus clearance (68–72)

  • IFNα therapeutic effective in control of HCV, but highly inflammatory (source)
Human immunodeficiency virus (+ssRNA Retroviridae)

  • IFNλ1, 2, 3 treatment of human monocyte-derived macrophages inhibits infection via JAK–STAT (73, 74)

  • Pretreatment of human primary CD4 T cells with IFNλ1 or IFNλ2 reduced HIV integration and posttranscriptional events, but IFNλ1 was not negatively correlated with HIV levels in vivo (75)

  • Type I IFN can inhibit HIV in vivo in a humanized murine mouse model of infection (76)

  • High, sustained type I IFN associated with pathogenicity during SIV infection of rhesus macaques (77)

  • Serum IFNα inversely correlates with CD4 T cell counts in human patients with HIV-1 (78)
Norovirus (+ssRNA Caliciviridae)

  • Recombinant IFNλ clears persistent norovirus infection in a murine model, dependent upon IFNλR signaling in intestinal epithelial cells (IECs) (34, 50, 79)

  • Mice lacking IFNλR have increased titers and virus shedding (50)

  • Persistence of norovirus in mice lacking IFNAR specifically on CD11c+ cells (80)
Rhinovirus (+ssRNA Picornaviridae)

  • IFNλ levels inversely correlate with rhinovirus replication in a human bronchial epithelial cell line (81)

  • Type I IFN response contributes to control of rhinovirus in murine airway cells at 37° (82)
SARS coronavirus (+ssRNA Coronaviridae)

  • IFNλR−/− mice have increased viral titers and shedding (49)

  • Type I IFN signaling in hematopoietic cells drives SARS-CoV pathogenesis in a murine model (83)
West Nile virus (+ssRNA Flavi)

  • Treatment with IFNλ protects mice from lethal infection

  • IFNλR−/− mice have increased permeability of the blood–brain barrier and neuroinvastion of virus (84)

  • Mice lacking IFNAR have enhanced viral loads, increased tropism, and complete mortality (85)
Zika virus (+ssRNA Flaviviridae)

  • Knock down of IFNλR in HBMECs leads to increase in ZIKV dsRNA (86)

  • Mice lacking IFNAR susceptible to Zika virus infection (87)

  • Zika virus antagonizes type I IFN response in human DCs (88)
Double stranded RNA viruses
Reovirus (dsRNA Reoviridae)

  • Fatal disease in neonatal mice lacking IFNλR

  • Mice lacking IFNλR fully or specifically in IECs have increased virus shedding and growth in IECs (34, 89)

  • No enhanced disease or systemic spread in IFNAR−/− mice infected intracranially (90)
Rotavirus (dsRNA Reoviridae)

  • IFNλ treatment (synergistically with IL-22) reduces rotavirus titer (91)

  • Mice lacking IFNλR have increased virus titer (30)

  • Minimal role for IFNAR signaling in control of viral disease in mice (89)
DNA viruses
Cytomegalovirus (dsDNA Herpesviridae)

  • IFNλ reduces replication and CD4 T cell proliferation in human PBMCs (92)

  • Type I IFN released by DCs inhibits replication (93)

  • CMV directly inhibits type I IFN (94)
Hepatitis B virus (dsDNA Hepadnaviridae)

  • Restricts virus in murine cell line (32)

  • Pegylated IFNλ augmented antiviral reduction in hepatitis B virus (HBV) levels of infected patients (95)

  • Type I IFN restricts HBV in hepatocytes (96)

  • HBV inhibits type I IFN induction (97, 98)
Herpes simplex virus (HSV) (dsDNA Herpesviridae)

  • IFNλ inhibits HSV-1 and HSV-2 in human epithelial cells (99, 100)

  • SNP rs12979860 correlates with HSV-1 severity upon reactivation (101)

  • INFAR−/− adult mice are susceptible to infection of the choroid plexus and HSV encephalitis, similar to newborn WT (102)