David CameriniAssistant Professor, Molecular Biology and Biochemistry |
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Research Interests |
Molecular Biology and Pathogenesis of HIV-1 | |
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Research Abstract |
AIDS is currently a leading cause of death 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 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, dual tropic (R5X4) or CXCR4 tropic (X4), 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 have made progress in this area using thymic organ culture. 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 signalling 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 the innate antiviral proteins known as defensins. Several defensins block HIV-1 replication by mechanisms that are not well charcterized. Understanding these mechanisms may shed light on viral pathogenesis and lead to new treatments for AIDS. |
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| Publications | Pathogenesis of primary R5 HIV-1 clones in SCID-hu mice, Scoggins RM, Taylor, JR Jr, Patrie J, van’t Wout, A, Schuitemaker, H, Camerini, D, J. Virol, 2000, , 3205- 3216 | |
| Expression and function of chemokine receptors on human thymocytes: Implications for infection by HIV-1, Taylor JR Jr, Kimbrell K, Scoggins R, Wu L and Camerini, D, J. Virol, 2001, 75: 8752-8760 | ||
| ADP strongly potentiates the ability of the chemokines MDC, TARC and SDF-1 to stimulate platelet function, Gear ARL, Suttitanamongkol S, Viisoreanu D, Polanowska-Grabowska RK, Raha S and Camerini D, Blood, 2001, 97: 937-945 | ||
| Platelet chemokines and chemokine receptors: linking hemostasis, inflammation and host defense, Gear ARL, and Camerini D, Microcirculation 2003, 10: 335-350 | ||
| Requirement for the second coding exon of Tat in the optimal replication of macrophage-tropic HIV-1, 20. Neveut C, Scoggins R, Camerini D, Markham R and Jeang K-T, J. Biomed. Sci. 2003, 10: 651-660 | ||
| HIV-1 Vpr-mediated G2 arrest requires RAD17 and Hus1 and induces nuclear BRCA1 and g-H2AX foci formation, Zimmerman E, Chen J, Andersen J, Ardon O, DeHart J, Blackett J, Choudhary S, Camerini D, Nghiem P and Planelles V, Mol and Cell Biol. 2004, 24: 9286-9294 | ||
| R5 HIV-1 Infection of Fetal Thymic Organ Culture Induces Cytokine and CCR5 Expression; Components of a Pathogenic Pathway, Choudhary S, Kimbrell K, Colasanti J, Kwa D, Schuitemaker H and Camerini D, In press | ||
| HIV-1 mediated signal transduction through CCR5 allows infection of resting memory T cells, Vasudevan J, Matthews A, O’ Connor C, Meek A and Camerini D, Submitted | ||
| Cytopathic determinants of primary R5 HIV-1 clones, Scoggins RM, Olivieri K, Matthews A, Brodrick B, Taylor JR Jr, Chernauskas D and Camerini D, In preparation | ||
| Graduate Programs |
Virology Immunology and Pathogenesis Biotechnology |
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| Research Center | Center for Virus Research, Center for Immunology | |
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=4930 | |
| Last updated | 10/14/2004 | |