Charles Wood, PhD
HIV and Kaposi’s Sarcoma Associated Herpesvirus Pathogenesis Acquired immune deficiency syndrome (AIDS) is a devastating disease that is caused by a retrovirus known as the human immunodeficiency virus (HIV). Infected individuals are not only immunosuppressed but also frequently develop malignancies, such as lymphomas and Kaposi’s sarcoma. The Wood laboratory has been involved in the molecular biology of HIV and a recently identified human herpesvirus associated with Kaposi’s sarcoma (KS) named KSHV. KSHV has been linked to HIV and Kaposi’s sarcoma but its route of transmission and whether infection by this virus can directly cause KS are not known. Dr. Wood’s laboratory has found that the infection rate is extremely high in Zambia, a central African nation that lies in the heart of the AIDS epidemic. Dr. Wood’s study involves the recruitment of mother/infant pairs at birth to determine (1) the seroprevalence for HIV and KSHV, (2) whether KSHV DNA can be found in infants’ blood, and (3) to determine the source of vertical and/or horizontal transmission. One of the laboratory’s findings is that HIV infects 30% of Zambia’s normal female population and 40% are infected by KSHV. Therefore, the implications for disease development and transmission of both HIV and KSHV to babies are enormous. Given this high incidence of infection, the Wood lab has been studying whether KSHV can be transmitted from mothers to their newborns, whether infected children will develop KS, and whether HIV is a co-factor for transmission. The laboratory has also found that almost all Zambian HIV are of subgroup C and are rapidly spreading in Zambia. Unfortunately, very little is known about subgroup C’s viral biological properties, pathogenesis, and genetic evolution in infected individuals. Dr. Wood has been characterizing a panel of subtype C HIV isolated from infected infants at various time points after birth to understand the natural evolution of these viruses and to correlate them to disease progression. The goal of these studies is to better understand the biology of this virus and its transmission so that strategies can be developed to block its transmission. Studies are now underway to generate a chimeric virus between the subtype C HIV-1 and a simian immunodeficiency virus so that an animal model can be generated to test various strategies to block vertical HIV transmission. Another focus of the Wood laboratory is the control of KSHV replication at the molecular level. KSHV characteristically establishes latent infections in target cells where viral gene expression is highly limited and tightly controlled. The virus can then periodically reactivate to go through lytic replication. Although latent infection may play a role in sustained viral infection and tumorigeneisis, lytic reactivation has been implicated to be important for KS development. Therefore, the understanding of how the virus maintains latency and of the viral genes involved is of significance. The laboratory has been studying a viral gene called “Regulator of Transcription Activation” (RTA), which is the central gene involved in the switch from latent to lytic replication. The laboratory has identified a cellular factor that interacts with RTA and enhances its transactivation function, and is actively deciphering the molecular mechanism involved in their interaction and transactivation of viral gene transcription. This study will lead to the development of strategies in preventing the virus from going through lytic replication and KS development. Selected Recent Articles: 1. Santhi G., H. Sneller, L. Walters, J. G. Sharp, S. J. Pirruccello, J. T. West, C. Wood, S. Dewhurst, H.E. Gendelman, and L. Poluektova. HIV-1 pathobiology studied in humanized Balb/c-Rag2-/- 2. Yang, Z., and C. Wood. The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus. J Virol 81:6294-306, 2007. 3. Ng'andwe, C., J. J. Lowe, P. J. Richards, L. Hause, C. Wood, and P. C. Angeletti. The distribution of sexually transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa. BMC Infect Dis 7:77, 2007. 4. Wojcicki, J.M., C. Kankasa, C. Mitchell and C. Wood. Traditional Practices and Exposure to Bodily Fluids in Lusaka, Zambia. J of Tropical Medicine and International Health, 12:150-5, 2007. 5. Zhang, H., F. Hoffmann, J. He, X. He, C. Kankasa, J. T. West, C. D. Mitchell, R. M. Ruprecht, G. Orti, and C. Wood. Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease. Retrovirology 3:73, 2006. 6. Song, R. J., A. L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, R. D. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P. L. Li, E. Shai-Kobiler, T. Wang, C. M. McCann, H. Zhang, C. Wood, C. Kankasa, W. E. Secor, H. M. McClure, E. Strobert, J. G. Else, and R. M. Ruprecht. Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env. J Virol 80:8729-38, 2006. 7. St Lawrence, J.S., W. Klaskala, C Kankasa, J .T. West, C. D. Mitchell and C. Wood. Factors Associated with HIV prevalence in a pre-partum cohort of Zambian women. Int J STD AIDS 17:607-13, 2006. 8. Bagasra, O., D. Patel, L. Bobroski, J. A. Abbasi, A. U. Bagasra, H. Baidouri, T. Harris, A. El-Roeiy, Z. Lengvarszky, H. Farzadegan, and C. Wood. Locatization of human herpesvirus type 8 in human sperms by in situ PCR. J Mol Histol:1-12, 2006. 9. Wood, C. and Harrington, W., Jr. AIDS and associated malignancies. Cell Res 15(11-12):947-952, 2005. 11. Zhang, H., Hoffmann, F., He, J., He, X., Kankasa, C., Ruprecht, R., West, J. T., Orti, G., and C. Wood. Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant. J. Retrovirology 2:67, 2005. 12. Burkala, E.J., J. He, J.T. West, C. Wood, and C.K. Petito. Compartmentalization of HIV-1 in the central nervous system: role of the choroid plexus. AIDS 19:675-84, 2005. |
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c-/- mice. J Virol 81:2700-12, 2007.
