| First Author | Lee AG | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 5 | PubMed ID | 32161194 |
| Mgi Jnum | J:287315 | Mgi Id | MGI:6415878 |
| Doi | 10.1172/jci.insight.134258 | Citation | Lee AG, et al. (2020) T cell response kinetics determines neuroinfection outcomes during murine HSV infection. JCI Insight 5(5) |
| abstractText | Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear. In this study, we show that vaginal infection of mice with HSV-1 leads to the rapid appearance of mature DCs in the draining lymph node, which is dependent on an early burst of NK cell-mediated IFN-gamma production in the vagina that occurs after HSV-1 infection but not HSV-2 infection. Rapid DC maturation after HSV-1 infection, but not HSV-2 infection, correlates with the accelerated generation of a neuroprotective T cell response and early accumulation of IFN-gamma-producing T cells at the site of infection. Depletion of T cells or loss of IFN-gamma receptor (IFN-gammaR) expression in sensory neurons both lead to a marked loss of neuroprotection only during HSV-1, recapitulating a prominent feature of HSV-2 infection. Our experiments reveal key differences in host control of neuronal HSV-1 and HSV-2 infection after genital exposure of mice, and they define parameters of a successful immune response against genital herpes. |
