Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover

Subudhi, Sonu; Rapin, Noreen; Misra, Vikram

Several factors may alter long-term, low-level viral persistence in bats. Suppression of the immune response holding active virus replication in check would allow the virus to replicate to higher levels. This could happen in stressful conditions that affects the immune system. In other animals, a variety of stressors lead to reactivation of latent herpesviruses as reviewed by Grinde [48, 49] . In neurons latently infected by herpes simplex virus -1 (HSV-1), viral replication is inhibited by the recruitment of CD8 + T cells which secrete interferon-γ (IFN-γ) and suppress viral transcription factors via noncytolytic granzyme mediated degradation [50] . During stress, there is a reduction of HSV-specific CD8 + T cells capable of producing IFN-γ. This contributes to reactivation of the virus [51] . Studies on murine gammaherpesvirus-68 (MHV-68) in mice have shown that latent gammaherpesviruses are sequestered in cells in the spleen and can be reactivated by stress [52, 53] . Stressors, such as unfolded protein responses and hypoxia, can induce the expression of viral immediate early genes that help in initiating the lytic cycle of virus thereby reactivating it [54] .