Unwanted guests: How herpes simplex virus gets rid of the cell’s security guards

Unwanted guests: How herpes simplex virus gets rid of the cell's security guards

Herpes simplex virus 2 (HSV-2) is the primary cause of genital herpes, which is one of the most common sexually transmitted viral infections worldwide and a major cofactor for human immunodeficiency virus infection. In some aspects, the invention relates to methods for treating a subject having a cancer stem cell by administering to the subject an oncolytic Herpes virus. 235-239; Olofsson, S. The assay system relies on expression of the reporter gene driven by a specific viral promoter that is triggered early in the course of viral infection. To benefit from the GVL effects from DLI and prevent severe GVHD, donor T cells will be transduced in vitro with a retroviral vector carrying the Herpes Simplex Virus thymidine kinase (HSV-Tk) suicide gene and the gene encoding a truncated (non-functional) form of the low affinity nerve growth factor receptor (NGF-R). “We reasoned that viral DNA would be recognized by the cell’s DNA repair machinery and that the virus must somehow manipulate the cell’s response to this foreign DNA,” explains Weitzman. , and Kubicek, H.

These antisera inhibit in a similar fashion the purified herpesvirus-induced or vaccinia virus-induced DNA polymerase isolated from infected cells. In vivo administration of G1 or G2 peptide as a prophylactic eye drop completely blocked HSV-1 spread in the mouse cornea as evident by immunohistochemistry. “The virus effectively overrides the cell’s DNA damage response in order to prevent its own DNA from being recognized,” says Weitzman. Only 20 percent of herpes seropositive persons have symptomatic infection. They discovered that it flags for destruction two important DNA “security guards,” the proteins called RNF8 and RNF168, thereby taking out the DNA damage response in human cells in one big swipe. C8166 cells … With RNF8 and RNF168 safely out of the way, the virus can begin to take over.
Unwanted guests: How herpes simplex virus gets rid of the cell's security guards

Delving deeper, the team looked at the role of these DNA “security guards” that are singled out by ICP0. Surprisingly, RNF8 and RNF168 also leave ubiquitin tags, but in this case, they mark regions of damage. They tag a protein called histone H2A, which directs DNA damage response proteins to accumulate at the sites of damage. The Salk team discovered that by removing RNF8 and RNF168, the viral ICP0 protein results in a decrease to the tag on the cellular H2A protein. The findings highlight the importance of these histone marks in DNA damage. “By identifying how HSV dismantles the host’s defense systems, we are shown the key steps, not only in viral infections, but also in the human DNA damage response,” Weitzman explains. HSV may have evolved this weapon because our cells use histone ubiquitination to try to silence gene expression from the viral DNA.

To date, the cellular internalization mechanism of VP22 fusion proteins is but little understood. 61/383,520, filed Sep. is now at Rice University, Houston); Stephanie Panier and Daniel Durocher from the Samuel Lunenfeld Research Institute, Mount Sinai Hospital in Toronto, Canada; Chris Boutell and Roger D. Everett at the University of Glasgow, UK; and Grant S. Stewart at Birmingham University, UK. The Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

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