Table 1. Summary of Immune Responses in Humans during Hantavirus Infection.
Categorical Response | Immune Marker | Effect of Infection | Virus Speciesa | In Vitro/In Vivo | Tissue or Cell Typeb, Phase of Infectionc | References |
Innate | RIG-I | Elevated | SNV | In vitro | HUVEC, ≤24 h p.i. | [79] |
Reduced | NY-1V | In vitro | HUVEC, ≤24 h p.i. | [37] | ||
TLR3 | Elevated | SNV | In vitro | HUVEC, ≤24 h p.i. | [79] | |
IFN-β | Elevated | PUUV, PHV, ANDV | In vitro | HSVEC, HMVEC-L, ≤24 h p.i. | [36],[80] | |
Reduced | TULV, PUUV NSs | In vitro | COS-7 and MRC5 cells, ≤24 h p.i. | [32],[33] | ||
IFN-α | Elevated | PUUV, HTNV | In vitro | MФ, DCs, 4 days p.i. | [30] | |
No change | HTNV | In vivo | Blood, acute | [81] | ||
IRF-3, IRF-7 | Elevated | SNV, HTNV, PHV, ANDV | In vitro | HMVEC-L, ≤24 h p.i. | [33],[38] | |
MxA | Elevated | HTNV, NY-1V, PHV, PUUV, ANDV, SNV, TULV | In vitro | MФ,HUVEC,HMVEC-L, 6 h–4 days p.i. | [36], [39]–[41],[79] | |
MHC I and II | Elevated | HTNV | In vitro | DCs, 4 days p.i. | [30] | |
CD11b | Elevated | PUUV | In vivo | Blood, acute | [82] | |
CD40, CD80, CD86 | Elevated | HTNV | In vitro | DCs, 4 days p.i. | [30],[83] | |
NK cells | Elevated | PUUV | In vivo | BAL, acute | [84] | |
Proinflammatory/Adhesion | IL-1β | Elevated | SNV, HTNV | In vivo | Blood, lungs, acute | [85],[86] |
IL-6 | Elevated | SNV, PUUV | In vivo | Blood, lungs, acute | [85],[87],[88] | |
TNF-α | Elevated | PUUV, SNV, HTNV | In vivo | Blood, lungs, kidney, acute | [85],[86],[88],[89] | |
Elevated | HTNV | In vitro | DCs, 4 days p.i. | [30] | ||
CCL5 | Elevated | SNV, HTNV | In vitro | HMVEC-L, HUVEC, 12 h–4 days p.i. | [38],[39],[90] | |
CXCL8 | Elevated | PUUV | In vivo | Blood, acute | [82] | |
Elevated | PUUV | In vivo | Men, blood, acute | [62] | ||
Elevated | TULV, PHV, HTNV | In vitro | HUVEC, MФ, 2–4 days p.i. | [39],[91] | ||
CXCL10 | Elevated | SNV, HTNV, PHV | In vitro | HMVEC-L,HUVEC, 3–4 days p.i. | [38],[39] | |
Elevated | PUUV | In vivo | Men, blood, acute | [62] | ||
IL-2 | Elevated | SNV, HTNV, PUUV | In vivo | Blood, lungs, acute | [82],[86] | |
Nitric oxide | Elevated | PUUV | In vivo | Blood, acute | [92] | |
GM-CSF | Elevated | PUUV | In vivo | Women, blood, acute | [62] | |
ICAM, VCAM | Elevated | PUUV | In vivo | Kidney, acute | [87] | |
Elevated | HTNV, PHV | In vitro | HUVEC, 3–4 days p.i. | [30],[39] | ||
E-selectin | Elevated | PUUV | In vivo | Blood, acute | [82] | |
CD8+ and CD4+ T cells | IFN-γ | Elevated | HTNV, SNV | In vivo | Blood, CD4+,CD8+, lungs, acute | [81],[86] |
CD8+ | Elevated | DOBV, PUUV, HTNV | In vivo | Blood, BAL, acute | [52],[84],[93] | |
Virus-specific IFN-γ+CD8+ | Elevated | PUUV, SNV | In vivo | PBMC, acute | [45],[94] | |
Perforin, Granzyme B | Elevated | PUUV | In vivo | Blood, acute | [95] | |
CD4+CD25+ “activated” | Elevated | DOBV, PUUV | In vivo | PBMC, acute | [89],[93] | |
IL-4 | Elevated | SNV | In vivo | Lungs, acute | [86] | |
Regulatory | “suppressor T cells”d | Reduced | HTNV | In vivo | Blood, acute | [52] |
IL-10 | Elevated | PUUV | In vivo | Blood, acute | [86] | |
TGF-β | Elevated | PUUV | In vivo | Kidney, acute | [89] | |
Humoral | IgM, IgG, IgA, IgE | Elevated | All hantaviruses | In vivo | Blood | [4] |
SNV, Sin Nombre virus; NY-1V, New York-1 virus; PUUV, Puumala virus; PHV, Prospect Hill virus; ANDV, Andes virus; TULV, Tula virus; HTNV, Hantaan virus; DOBV, Dobrava virus.
HUVEC, human umbilical vascular endothelial cells; HSVEC, human saphenous vein endothelial cells; HMVEC-L, human lung microvascular endothelial cells; COS-7, African green monkey kidney fibroblasts transformed with Simian virus 40; MRC5, human fetal lung fibroblasts; MФ, macrophages; DCs, dendritic cells; BAL, bronchoalveolar lavage, PBMC, human peripheral blood mononuclear cells.
Acute infection is during symptomatic disease in patients.
Suppressor T cells likely represent cells currently referred to as regulatory T cells.