NUCLEAR PORE

Baylor College Of Medicine, Houston TX

Investigators

Linked publications & trials

Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Herpes Simplex Virus (HSV) infects almost 2 billion people worldwide, due in part to its low mortality rate and its ability to cause latent infections. HSV is an enveloped, dsDNA virus. Infection of host cells begins with binding of HSV to the cell membrane, after which the HSV capsid and some bound tegument proteins are released into the cytoplasm using either a direct membrane fusion or a pH-dependent endocytosis pathway. Once in the cytoplasm, HSV travels along microtubules towards the nucleus. Upon reaching the nucleus, the capsid interacts with Nuclear Pore Complex (NPC) filaments (Nup214-Nup88 and/or Nup358) emanating from the NPC. Subsequently HSV releases its dsDNA genome at which point the dsDNA is translocated through the NPC. We hypothesize that structural studies will elucidate the method by which binding to the NPC causes the subsequent release and translocation of the viral genome. Using cryo-electron tomography, we will examine how HSV interacts with the NPC in Xenopus Laevis oocytes. Ultimately, the information from this study may aid in the development of better anti-viral drugs against HSV while helping researchers gain insight into the mechanisms other viruses employ for NPC attachment and genome translocation into the nucleus.