Jennifer LaVail, PhD, Professor
lavailj@vision.ucsf.edu
Administrative Assistant: 415-476-1861
LaVail Lab Website

Mutant Strains of Herpes Simplex Virus used as Probes
for Studying Axonal Transport

My research focuses on the mechanisms that neurotropic viruses use to enter and exit infected neurons. A critical step in the transmission of Herpes simplex virus type 1 virus (HSV) from one infected neuron to the next neuron is the polarized anterograde axonal transport of viral DNA from the host infected nerve cell body to the axon terminal for subsequent release. How the virus is transported and what viral proteins are necessary are long-standing questions. Using the HSV infected murine retinal ganglion cell model and a mutant strain of HSV that lacks the Us9 protein, we have found that HSV Us9 protein is necessary specifically for long distance anterograde axonal transport of viral capsid and DNA. It is unnecessary for retrograde axonal transport. We have also found that Us9 protein associates with VP5, the major capsid protein and is transported independently of viral envelope. Thus, the axonal transport of HSV DNA and capsid does not require the envelope. Thus, the axonal transport of HSV DNA and capsid does not require the traditional membrane vesicle proteins that associate with motors. Us9 protein is a potential therapeutic target specifically against encephalitic spread of HSV. Furthermore, as a model of non-vesicular transport, the anterograde axonal transport of HSV nucleocapsid offers a new biochemical tool for understanding this functional process in normal neurons.

Complete list of Publications/PubMed

Selected Publications

LaVail, J.H., A.N. Tauscher, A. Sucher, O. Harrabi and R. Brandimarti. The Us9 tegument proteins of HSV-1 is necessary for efficient anterograde transport of capsid and DNA in neurons in vivo. (Neuroscience. 2007 Mar 21; [Epub ahead of print]).

Duffy C., LaVail J.H., Tauscher A.N., Wills E.G., Blaho J.A., Baines J.D. Characterization of a UL49-null mutant: VP22 of herpes simplex virus type 1 facilitates viral spread in cultured cells and the mouse cornea. J. Virol. 80 (17): 8664-75, 2006.

LaVail, J.H., Tauscher, A.N., Hicks, J.W., Harrabi, O., Melroe, G.T. and D.M. Knipe. Genetic and molecular in vivo analysis of herpes simplex virus assembly in murine visual system neurons. J. Virol. 79 (17): 11142-11150, 2005.

LaVail, J.H., Tauscher, A.N., Aghaian, E., Harrabi, O., Sidhu, S.S. Axonal transport and sorting of herpes simplex virus components in mature mouse visual system. J. Virol. 77 (11), 6117-6126, 2003.

Ohara, P.T., Tauscher, A.N., and J.H. LaVail. Two paths for dissemination of herpes simplex virus from infected trigeminal ganglion to the murine cornea. Brain Res. 899 (1/2): 260-263, 2001.

Bearer, E.L., Breakefield, X.O., Schuback, D., Reese, T.S. and J.H. LaVail. Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument. P.N.A.S. USA, 97 (14): 8146-815, 2000.