Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons

Abstract

Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8+ T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8+ T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8α monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8+ T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8+ T cells aborting virion production.

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

“…The different regulation of DNA fragmentation and cell lysis emphasizes this point, and it remains unclear which, if either, of these processes most closely correlates with efficient control of viral replication. Furthermore, a prelytic halt of HSV replication has been described by CTL (46), and it was recently shown that CD8 ϩ CTL can control viral gene expression and reactivation from neurons without lysis of these cells (47). This effect was suggested to be mediated through the action of IFN-␥.…”

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

“…In a HSV latency mice model, cytotoxic T lymphocytes producing IFN-γ were shown to be able to prevent reactivation from latency in sensory neurons [116]. Another study concluded that IFN-α and -γ act as control factors of recurrent herpetic lesions [133].…”

Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia

“…Innate immunity involving macrophages and ␥␦ T cells contribute to the control of early viral replication in ganglia during acute infection (15,16). In the latent phase, infiltrating virus-specific CD8 ϩ T cells inhibit HSV-1 reactivation by means of IFN-␥ or cytolytic effector molecules such as perforin and granzyme B (grB) (17)(18)(19).…”