Role of IFN-gamma and tumor necrosis factor-alpha in herpes simplex virus type 1 infection.
One of the characteristics of herpes simplex virus type 1 (HSV-1) is that recurrent diseases often develop from latent infection established after acute infection. Cytokines have been proposed to play an important role in each stage of HSV-1 infection, but the exact role of cytokines remains unclear. In the present study, we investigated the role of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in acute infection and reactivation using IFN-gamma gene knockout (IFN-gamma(-/-)) mice and TNF-alpha gene knockout (TNF-alpha(-/-)) mice. We first examined the survival rate after corneal infection with HSV-1. The survival rates of wild-type C57BL/6 (B6) mice, IFN-gamma(-/-) mice, and TNF-alpha(-/-) mice were 97% (73 of 75), 57% (24 of 42), and 83% (60 of 72), respectively. These results suggest that TNF-alpha and IFN-gamma play a protective role in acute infection with HSV-1. We also examined the rate of reactivation induced by ultraviolet (UV) light in latently infected mice over 60 days postinoculation. The reactivation was confirmed by detecting viral DNA extracted from eyeballs by the polymerase chain reaction (PCR) method at day 2 after the UV light stimulation. The rates of reactivation in IFN-gamma(-/-) mice and TNF-alpha(-/-) mice were significantly higher than that in B6 mice; 16% (4 of 25) showed reactivation in B6 mice, 47% (9 of 19) in IFN-gamma(-/-) mice, and 48% (10 of 21) in TNF-alpha(-/-) mice. These results suggest that IFN-gamma and TNF-alpha play an important role in acute infection and reactivation from latency.
Minami
Masato
M
Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. minami@basic.kpu-m.ac.jp
Kita
Masakazu
M
Yan
Xiao-Qun
XQ
Yamamoto
Toshiro
T
Iida
Tohko
T
Sekikawa
Kenji
K
Iwakura
Yoichiro
Y
Imanishi
Jiro
J
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D002470:Cell Survival; D002522:Chlorocebus aethiops; D003315:Cornea / Q000378:metabolism / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014466:Ultraviolet Rays; D014709:Vero Cells; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma