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INSTITUTE FOR IMMUNOLOGY FACULTY
| David Camerini, Ph.D. |
| Fields of Study: |
| Pathogenesis, Viral Immunity |
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| Research Interests: |
| Molecular Biology and Pathogenesis of HIV-1
AIDS is currently a leading cause of death in the in the United States and a major cause of morbidity and mortality worldwide. The latest estimates indicate that about one million Americans and over forty million people worldwide are infected with HIV-1. Despite the introduction of better treatments for AIDS in the developed world, there is still a need for research and development relating to the mechanisms of HIV-1 pathogenesis and new methods of inhibiting the development of AIDS.
During the last few years we have focused our efforts on understanding the pathogenesis of CCR5 tropic strains of HIV-1 (R5 HIV-1) and on the selection for and maintenance of R5 HIV-1 following viral transmission, and during the first few years of infection. These topics are of crucial importance to an understanding of HIV-1 pathogenesis since R5 HIV-1 is predominant in infected individuals. We use normal human lymphocytes, tonsil and lymph node organ cultures to realistically study HIV-1 infection of the mature immune system. We also study HIV-1 infection of the thymus, an important aspect of AIDS, using SCID mice bearing human thymic grafts (SCID-hu mice), and fetal thymic organ culture. These systems, which maintain the complexity of lymphoid tissue, are ideal for our studies of HIV-1 pathogenesis since they accurately mimic the in vivo situation.
When HIV-1 is isolated from patients early in the course of infection it is typically CCR5 tropic, replicates relatively poorly and is not very cytopathic. In contrast, HIV-1 isolated from AIDS patients may be R5, R5X4 or CXCR4 tropic, but usually replicates more efficiently and is more cytopathic. We have taken advantage of this evolution of HIV-1 within infected individuals to map the determinants of HIV-1 mediated cytopathic effects (CPE) of AIDS associated R5 HIV-1. We are also determining the mechanisms of HIV-1 mediated CPE on infected cells and bystander cells. We find that HIV-1 infection of fetal thymic organ culture induces cytokine expression. Some of these cytokines, in turn, induce CCR5 expression, which allows further viral replication and CPE.
Another recent focus of our work has been to understand why R5 HIV-1 is selected following viral transmission, even when the transmitting individual also possesses the more pathogenic R5X4 or X4 HIV-1 types. A related question is why R5 HIV-1 strains are maintained during the long asymptomatic phase of HIV-1 infection when R5X4 or X4 mutants may frequently arise. Our recent data strongly suggest that HIV-1 mediated signaling through CCR5 allows infection of resting memory CD4+ T cells, which are crucial targets of HIV-1 infection.
Other interests in the lab include the mechanisms of action of natural antiviral proteins including defensins and CEM–15. Both block HIV-1 replication by unknown mechanisms. Understanding these mechanisms may shed light on viral pathogenesis and lead to new treatments for AIDS. |
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| Office Address/Phone: |
3213 McGaugh Hall
(949) 824-3381 |
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| Lab Address/Phone: |
3103 McGaugh Hall
(949) 824-1502 |
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| Email: dcamerin@uci.edu |
| Web Site: http://www.faculty.uci.edu/scripts/UCIFacultyProfiles/detailMBB.cfm?ID=4930 |
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