Yearbook 01


Pamela Mundt
Home Institution Ruprecht-Karls-Universität, Heidelberg Host Institution Gladstone Institute of Virology and Immunology, University of California, San Francisco Mentors: 1) Warner C. Greene, M.D.,Ph.D., Professor of Medicine and of Microbiology and Immunology Gladstone Institute of Virology and Immunology, UCSF; 2) Michael Sherman, M.D.,Ph.D. E-Mail pmundt@gmx.de
Research Topic see Abstract
Personal Reactions to the U.S. Experience The Gladstone Institute turned out to be a very enriching experience. Not only do I have the opportunity to participate in several projects in the laboratory learning different techniques, but I can also attend a vast academic program of journal clubs, scientific presentations and lecture cycles. San Francisco is a great city with a very international and liberal atmosphere. The Californian climate makes it a perfect place for outdoor activities. I had a lot of fun skiing in Tahoe, biking and hiking in the area and hanging around in parks. Apart from that, it offers interesting museums, exotic restaurants and a great nightlife. I am really enjoying my stay and I am looking forward to the summer.
Greatest Difficulties Encountered For my application to start the practical year next summer I needed to get a measles titer and a PPD done. To find a clinician who was willing to do that was not as easy as I thought it would be. At the Student Health Service they told me I was "an employee rather than a student," at the UCSF Employee Health Department, on the contrary, I seemed to be a student. At the fourth institution I went to they gave me a measles booster, because they were not allowed to draw blood.
Most humorous incident We certainly had a lot of fun staying at a cheap Motel in Santa Barbara for one night… (Sorry, that is only for the people at the West Coast!)
Helpful Hints for Future Students I wouldn't bother to look for apartments before arriving. Housing conditions are getting better at the moment. For the web-based search I would recommend: craigslist.com and UCSF homepage. To find out what is going on in San Francisco get the Guardian (available on every street corner for free) or check www.sfbg.com. If you like biking you should definitely buy a bike: craigslist.com or Targets (new, cheap, good) are helpful.
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Abstract on Research Topic:
HIV-infected lymphocytes display aberrant cell cycle profiles in vivo

Authors:
Michael. P. Sherman, ,J. A. Neidleman, P. Mundt, S. Williams, C. de Noronha, R. Grant, C. Kreis, M. Warmerdam, J. Kahn1, R. Hecht1, and Warner C. Greene*. Gladstone Institute of Virology and Immunology and 1Positive Health Program at San Francisco General Hospital, UCSF, San Francisco, CA

Background:
The HIV-1 accessory protein Vpr enhances HIV replication in macrophages and, when over-expressed in cultured primate cell lines, induces G2 cell cycle arrest. While it is hypothesized that arrest enhances viral replication, the demonstration of such cell cycle perturbation in the absence of Vpr overexpression has not been clearly demonstrated. Furthermore, it is unknown whether HIV-infected target cells in vivo display an abnormal cell cycle progression.

Methods:
We are now able to identify HIV-infected cells expressing viral proteins at the appropriate levels by employing intracellular p24 and flow cytometry. We infected peripheral blood mononuclear cells (PBMC) from sero-negative donors utilizing isogenic NL4-3 molecular clones differing only in Vpr expression. We also stained circulating PBMC isolated directly from patients with primary HIV infection.

Results:
We find that cultured PBMC subjected to a spreading infection display G2 cell cycle arrest that is greatly augmented by the presence of Vpr. In the absence of Vpr, these cell cycle changes are markedly diminished and vary from donor to donor. Importantly, a significant proportion of the activated T cells circulating in the peripheral blood of HIV-infected patients are arrested or paused at the G2/M phase of the cell cycle. However, activated but uninfected T cells from these same patients display a normal cell cycle distribution Conclusion: These data thus provide the first evidence that HIV alters cell cycle progression in vivo, likely in a Vpr-dependent fashion. This arrest may play a role in not only virus production, but also in the accelerated T cell turnover observed in HIV-infected individuals.

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