Herpesviruses Modulates The Host Cell Apoptosis Pathway By Silencing The Transcription Of Histone1.2

Apoptosis is self-update and self-destruction in response to a variety of external stress, including DNA damage by radiation and viral infection. Apoptosis is also a programmed event of gene regulation during development, when cells become redundant deleting unwanted cells, and functions as an emergency response after radiation damage, teratogenesis casued by the activation of oncogenes or viral infection.Virus infection induced early cell death could severely limit viral-production, reduce or eliminate the virus spread of offspring in host cells. In order to ensure the survival of the latent viral genomic DNA and to ensure that herpesviruses finishes its lytic infection cycle, the virus must devise strategies to prevent apoptosis from occurring or happening too soon.H1.2is a variant linker histone, which plays an essential role in the transmitting nuclear apoptotic signal to mitochondria. In order to test whether herpes viruses modulate host apoptotic pathway by regulating H1.2, we studied HSV-1and HCMV infect cells, and found that infected cells have reduced levels of H1.2both at RNA and protein level based on qRT-PCR and western-blot results. To determine the mechanism of viral induced reduction of H1.2, we did ChIP-seq analyses using RNA Pol II antibodies in HSV-1infected human BJ cells. We found that RNA Polymerase II are eliminated from the histone H1.2locus after HSV-1infection. Other histone genes were unaffected. We use HSV-1and HCMV infect cells, do qRT-PCR and western-blot results confirmed this observation. This result suggests that Herpesviruses inhibits the transcription of histone H1.2to prevent apoptosis.H1.2exerts it s function during apoptosis by translocating from the nucleus to the cytoplasm, which later interact with bcl-2proteins in the mitochondria. We also examined whether nuclear to cytoplasm translocation of H1.2is also affected by HSV-1infection. We first used etoposide which can induce DNA double-strand break treat the cells, show that H1.2release from the nucleus. Immunofluorescence experiment shows that H1.2remain nuclear during HSV-1infection, suggesting that HSV-1may prevent the cytoplasmic release of H1.2.As HSV-1actively modulate host apoptotic response, it may be doing so by specific viral factors. In an attempt to search for these factors, found the ICP4, ICP22, ICP27and ICP34.5proteins which affect histone H1.2expression. The important experiment focused on the vector designated that contain the regulation of H1.2, use the dual luciferase reporter to find the mechanism of H1.2transcriptional inhibition in the future.