Research Interests

"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.

Recent Publications

• Ghosh, S. K., C. Wood, L. H. Boise, A. M. Mian, V. V. Deyev, G. Feuer, N. L. Toomey, N. C. Shank, L. Cabral, G. N. Barber and W. J. Harrington 2003. Potentiation of TRAIL-induced apoptosis in primary effusion lymphoma through azidothymidine-mediated inhibition of NF-kappa B. Blood 101(6): 2321-2327.
• Brayfield, B. P., S. Phiri, C. Kankasa, J. Muyanga, H. Mantina, G. Kwenda, J. T. West, G. Bhat, D. B. Marx, W. Klaskala, C. D. Mitchell and C. Wood 2003. Postnatal human herpesvirus 8 and human immunodeficiency virus type 1 infection in mothers and infants from Zambia. Journal of Infectious Diseases 187(4): 559-568.
• Zhang, H., G. Orti, Q. J. Du, J. He, C. Kankasa, G. Bhat and C. Wood 2002. Phylogenetic and phenotypic analysis of HIV type 1 env gp120 in cases of subtype C mother-to-child transmission. Aids Research and Human Retroviruses 18(18): 1415-1423.
• Liu, X. J., M. Jana, S. Dasgupta, S. Koka, J. He, C. Wood and K. Pahan 2002. Human immunodeficiency virus type 1 (HIV-1) Tat induces nitric- oxide synthase in human astroglia. Journal of Biological Chemistry 277(42): 39312-39319.
• McCarthy, M., J. He, D. Auger, R. Geffin, C. Woodson, C. Hutto, C. Wood and G. Scott 2002. Cellular tropisms and co-receptor usage of HIV-1 isolates from vertically infected children with neurological abnormalities and rapid disease progression. Journal of Medical Virology 67(1): 1-8.
• Chen, G. M., S. H. Wang, K. Xiong, J. Z. Wang, T. Ye, W. P. Dong, Q. Wang, Q. M. Chen, Y. Q. Geng, C. Wood and Y. Zeng 2002. Construction and characterization of a chimeric virus (BIV/HIV- 1) carrying the bovine immunodeficiency virus gag-pol gene. Aids 16(1): 123-125.
• Wang, S. Z., S. H. Liu, M. H. Wu, Y. Q. Geng and C. Wood 2001. Identification of a cellular protein that interacts and synergizes with the RTA (ORF50) protein of Kaposi's sarcoma- associated herpesvirus in transcriptional activation. Journal of Virology 75(24): 11961-11973.
• Wang, S., S. Liu, M. Wu, Y. Geng and C. Wood 2001. Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 ORF50 gene product contains a potent C-terminal activation domain which activates gene expression via a specific target sequence - Brief report. Archives of Virology 146(7): 1415-1426.
• Flebbe-Rehwaldt, L. M., C. Wood and B. Chandran 2000. Characterization of transcripts expressed from human herpesvirus 6A strain GS immediate-early region BU16-U17 open reading frames. Journal of Virology 74(23): 11040-11054.
• Pahan K, Liu X, McKinney M, Wood C, Sheikh F, and Raymond J. 2000. Expression of a dominant-negative mutant of p21ras inhibits induction of nitric oxide sythase an activation of NF-kB in primary astrocytes. J. Neurochem, 74(6):2288-2295