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. Thompson, J., MacMillan, M. Karen Boegler, K. Wood, C. Elder, J. and VandeWoude, S. 2011. Pathogenicity and Rapid Growth Kinetics of Feline Immunodeficiency Virus Are Linked to 3′ Elements PLoS ONE, published 26 Aug 2011.

2. Holguin A, Banda M, Willen EJ, Malama C, Chiyenu KO, Mudenda VC. and Wood C. 2011. HIV-1 Effects on Neuropsychological Performance in a Resource-Limited Country, Zambia. AIDS Behav. July (Epub ahead of print).

3. Lei, Y., Kgomotso Makhaola, K, Pittayakhajonwut, D., Wood, C. and Angeletti, P. 2011. Human Papillomavirus 16 Variants from Zambian women with Normal Pap Smears. J Med Virology 73(9):1085-92.

4. Constantino,A., Huang,Y., Zhang, Z., Wood, C. and Zheng, J. 2011. HIV-1 Clades B and C Exhibit Differential Infectivity: Relevance to Macrophage-Mediated Neurotoxicity. Neurotox Res. 2011 Oct;20 (3):277-88. Epub Feb 19.

5. Minhas, V., Crabtree, K., Chao, A., Wojcicki, J., Sifuniso, A., Nkonde, C., Kankasa, C., Mitchell, C. and Wood, C. 2011. The Zambia Children’s KS-HHV8 Study: Rationale, Study Design, and Study Methods. Am J of Epidemiology 73(9):1085-92.

6. Zhang T, Wang Y, Zhang L, Liu B, Xie J, Wood C, Wang J. 2011. Lysine Residues of Interferon Regulatory Factor 7 Affect the Replication and Transcription Activator-mediated Lytic Replication of Kaposi's Sarcoma-associated Herpesvirus/ Human Herpesvirus 8. J Gen Virol. 92:181-187.

7. Iordanskiy, S., Waltke., M., Feng, Y., Wood, C. 2010. Subtype-associated differences in HIV-1 reverse transcription affect the viral replication. Retrovirology. Oct 12;7(1):85. Epub ahead of print. PMCID in Process.

8. Zhang H., Tully, D.C., Zhang, T., Moriyama, H., Thompson, J., Wood, C. 2010. Molecular Determinants of HIV-1 Subtype C Coreceptor Transition from R5 to R5X4. Virology 407(1):68-79.

9. Gonzalez, S., Gondwe, C., Tully, D.C., Minhas, V., Shea, D., Kankasa, C., M’soka, T., and Wood, C. 2010. Anti-Retroviral Therapy Resistance Mutations Present in the HIV Type 1 Subtype C pol and env Regions from Therapy Naïve Patients in Zambia. AIDS Res and Human Retrovirus. 26:795-803.

10. Zhang, T., He, H., Ding, Y., Crabtree, K., Minhas, V., Wood, C. 2010. Prevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) in rural community with high risk for blood borne infections in central China. Clin Microbiol Infect. Jun 8 (Epub ahead of print)

11. Tully, D.C., Wood, C. 2010. Chronology and evolution of the HIV-1 subtype C epidemic in Ethiopia. AIDS. Jun 19;24(10):1577-82.

12. Robertson K, Liner J, Hakim J, Sankalé JL, Grant I, Letendre S, Clifford D, Diop AG, Jaye A, Kanmogne G, Njamnshi A, Langford TD, Weyessa TG, Wood C, Banda M, Hosseinipour M, Sacktor N, Nakasuja N, Bangirana P, Paul R, Joska J, Wong J, Boivin M, Holding P, Kammerer B, Van Rie A, Ive P, Nath A, Lawler K, Adebamowo C, Royal W 3rd, Joseph J. 2010 NeuroAIDS in Africa. J Neurovirol. Jun 16(3):189-202.

13. Wen, H.J., Yang, Z., Zhou, Y., Wood, C. 2010. Enhancement of autophagy during lytic replication by the Kaposi’s sarcoma-associated herpesvirus replication and transcription activator. J Virol. 84(15):7448-58. PMCID in Process.

14. Minhas, V., Brayfield, B.P., Crabtree, K.L., Kankasa, C., Mitchell, C.D., Wood, C. 2010. Primary gamma-herpesviral infection in Zambian children. BMC Infect Dis. May 12:10:155.

15. Yang Z and Wood C. 2010. The replication and transcription activator (RTA) of Kapsarcoma-associated herpesvirus/human herpesvirus-8. Frontiers in Biology, 5(2), 105-115.

16. Zhang, H., Rola, M., West, J, Tully, D., Kubis, P., He, J., Kankasa, C. and Wood, C. 2010. Functional Properties of the HIV-1 Subtype C Envelope Glycoprotein Associated with Mother to-Child Transmission. Virology May 10;400(2):164-74.

17. Zhang, H., Tully, D.C., Hoffmann, F.G., He, J., Kankasa, C., Wood, C. 2010. Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected Zambian infants. PLoS ONE, Feb 18:5(2):e9294.

18. K Bowa, K., Wood, C., Chao, A., Chintu, C., Mudenda, V. and Chikwenya, M A review of the epidemiology of cancers at the University Teaching Hospital, Lusaka, Zambia. 2009. Tropical Doctor, 39: 5-7.

19. Jaber, T., Bohl, C.R., Lewis, G.L., Wood, C., West, J.T. Jr., Weldon, R.A. Jr. 2009. Human Ubc9 contributes to the production of fully infectious HIV-1 virions. J Virol, 83(20):10448-59.

20. Tso, F.Y., Hoffmann, F.G., Tulley, D.C., Lemey, P., Rasmussen, R.A., Zhang, H., Ruprecht, R.M., Wood, C. 2009. A Comparative study of HIV-1 clade C env evolution in a Zambian infant with an infected rhesus macaque during disease progression. AIDS Sept 10; 23(14):1817-28.

21. Yang, Z., Wen, HJ., Minhas, V., Wood, C. 2009. The zinc finger DNA-binding domain of K-RBP plays an important role in regulating Kaposi's sarcoma-associated herpesvirus RTA-mediated gene expression. Virology Sep 1;391(2):221-31.

22. Wen HJ, Minhas V, Wood C. 2009. Identification and characterization of a new Kaposi's sarcoma-associated herpesvirus replication and transcription activator (RTA)-responsive element involved in RTA-mediated transactivation. J Gen Virol. Apr;90(Pt 4):944-53.

23. Siddappa, N.B., Song, R., Kramer, V.G., Chenine, A-L., Velu, V., Ong, H., Rasmussen, R. A., Grisson, R.D., Wood, C., Zhang, H., Kankasa, C., Amara, R.R., Else, J.G., Novembre, F.J., Montefiori, D.C., and Ruprecht, R. 2009. Neutralization-Sensitive R5-Propic Simian-Human Immunodefiency Virus HSIV-2873Nip, Which Carries env Isolated from and Infant with a Recent HIV Clade C Infection. J Virol 83(3); 1422-1432.

24. Kong, X., West, J.T., Shea, D.M., M’soka, T.J., Wood, C. 2008. The HIV-1 evelope confers higher replicative fitness to perinatally transmitted viruses. J Virol 82(23);11609-18.

25. Wojcicki, J., Mwanahamuntu, M., Minhas, V., Djokic, B., Kankasa, W., Brayfield, B., Phiri, S., Wood, C. and Mitchell, C. 2008. Mortality among HIV-1 and HHV-8 affected Mother-Infant pairs in Zambia. Cancer Epidemiology, Biomarkers & Prevention. 17(9):2238-43.

26. Minhas, V., Crabtree, K.L., Chao, A., M’soka, T.J., Kankasa, C., Bulterys, M., Mitchell, C.D., and C. Wood. 2008. Early Children Infection by Human Herpesvirus 8 in Zambia and the Role of Human Immunodefiency Virus Type 1 Coinfection in a Highly Endemic Area. Am J Epidemiol. 168(3):311-20.

27. Minhas, V., Crosby, L.N., Crabtree, K.L., Phiri, S., M’soka, T.J., Kankasa, C., Harrington, W.J., Mitchell, C.D. and C. Wood. 2008. Development of an immunoflourescent assay using recombinant proteins expressed in insent cells for the screening and confirmation of human herpesvirus 8 antibodies. Clin Vaccine Immunol. 15(8):1259-64.

28. Yang, Z., Yan., Z. and C. Wood. 2008. Kaposi’s sarcoma-associted herpesvirus transactivator RTA promotes degradation of the repressors to regulate viral lytic replication . J Virol. 82:3590-603.

29. Hoffman, F. G., He, X., West, J. T., Lemey, P., Kankasa, C. and C. Wood. 2008. Genetic variation in mother-child acute seroconverter pairs from Zambia. AIDS 23; 22:817-24.

30. 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. 2007. HIV-1 pathobiology studied in humanized Balb/c-Rag2-/-c-/- mice. J Virol 81:2700-12.

31. Yang, Z., and C. Wood. 2007. The transcriptional repressor K-RBP modulates RTA-mediated transactivation and lytic replication of Kaposi's sarcoma-associated herpesvirus. J Virol 81:6294-306.

32. Ng'andwe, C., J. J. Lowe, P. J. Richards, L. Hause, C. Wood, and P. C. Angeletti. 2007. The distribution of sexually transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa. BMC Infect Dis 7:77

33. Wojcicki, J.M., C. Kankasa, C. Mitchell and C. Wood. 2007. Traditional Practices and Exposure to Bodily Fluids in Lusaka, Zambia. J of Tropical Medicine and International Health, 12:150-5.

34. Zhang, H., F. Hoffmann, J. He, X. He, C. Kankasa, J. T. West, C. D. Mitchell, R. M.
Ruprecht, G. Orti, and C. Wood. 2006. Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease. Retrovirology 3:73.

35. 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. 2006. 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.

36. St Lawrence, J.S., W. Klaskala, C Kankasa, J .T. West, C. D. Mitchell and C. Wood. 2006. Factors Associated with HIV prevalence in a pre-partum cohort of Zambian women. Int J STD AIDS 17:607-13

37. 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. 2006. Locatization of human
herpesvirus type 8 in human sperms by in situ PCR. J Mol Histol:1-12.

38. Wood, C and Harrington, W, Jr. 2005. AIDS and associated malignancies. Cell Res 15(11-12):947-952.

39. Zhang, H., Hoffmann, F., He, J., He, X., Kankasa, C., Ruprecht, R., West, J. T., Orti, G., and C. Wood. 2005. Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant. J. Retrovirology 2:67.

40. Burkala, E.J., J. He, J.T. West, C. Wood, and C.K. Petito. 2005. Compartmentalization of
HIV-1 in the central nervous system: role of the choroid plexus. AIDS 19:675-84.

41. Cavacini, LA, Duval M, Patil A, Wood C, Mayer KH, Ruprecht RM, Posner MR. 2005.
Dichotomy in cross-clade reactivity and neutralization by HIV-1 sera: Implications for
active and passive immunotherapy. J Med Virol 76:146-52.

42. Zhang, J., J. Wang, C. Wood, and L. Zhang. 2005. KSHV/HHV-8 replication and transcription activator (RTA) regulates viral and cellular genes via ISRE. J Virol 79:5640-52.

43. Wang, J., Zhang, J., Zhang, L., Harrington Jr., W., West, J. T., and C. Wood. 2005. Modulation of human herpesvirus 8/Kaposi’s sarcoma-associated herpesvirus RTA transactivation by interferon regulatory factor 7. J. Virol. 79:2420-2431.

44. Klaskala, W., Brayfield, B.P., Kankasa, C., Bhat, G., West, J.T., Mitchell, C.D., and C. Wood. 2005. Epidemiological Characteristics of Human Herpesvirus-8 Infection in a Large Population Group of Antenatal Women. J. Med. Virol, 75:93-100.

45. Grisson, R. D., A. Chenine, L. Yeh, J. He, C. Wood, C. Kankasa, W. Xu, and R. Ruprecht. Infectious molecular clone of a recently transmitted pediatric HIV clade C isolate from Africa: Evidence of intra-clade recombination. 2004. J Virol. 2004; 78:14066-9.

46. Filgueira-Perez, D. M., B.P. Brayfield, S. Phiri, M.V. Borca, C. Wood, and T. J. Morris. 2004. Preserved antigenicity of HIV-1 p24 produced and purified in high yields from plants inoculated with a tobacco mosaid virus (TMV)-derived vector. J. Virological Methods. 121: 201-208.

47. Brayfield, B., Kankasa, J. West, J. Muyanga, G. Bhat, W. Klaskala, C. Mitchell, and C. Wood. 2004. Distribution of Kaposi SarcomaAssociated Herpesvirus/Human Herpesvirus 8 in Maternal Saliva and Breast Milk in Zambia: Implications for Transmission. J. Inf. Dis. 189:2260-70.

48. West J and C. Wood. 2003. The Role of Kaposi’s Sarcoma-Associated Herpesviruses/Human Herpesvirus-8 Regulator of Transcription Activation (RTA) in Control of Gene Expression. Oncogene 22:5150-5163.

Education

University of Kansas, Lawrence, KS
BA, Chemistry & Microbiology
1975

Columbia University, New York, NY
PhD, Microbiology
1981

Basal Institute of Technology
Postdoc, Molecular Immunology
1981

Massachusetts Institute of Technology, Cambridge, MA
Postdoc, Molecular Immunology
1983

Professsional Experience

1975-81
Research Assistant, Laboratory of Professor Elvin A Kabat; Dept. of Microbiology
Columbia University College of Physicians and Surgeons, New York, NY

1981-1983
Research Associate in the Laboratory of Professor Susumu Tonegawa
Massachusetts Institute of Technology, Cambridge, MA

1983-1985
Staff Scientist (Group Leader), Molecular Immunologist, Cancer Research and Molecular Biology Department
Abbott Labs, North Chicago, IL

1984-1985
Adjunct Assistant Professor, Department of Biochemistry, Molecular Biology and Cell Biology
Northwestern University, Evanston, IL

1985-1989
Assistant Professor, Department of Microbiology
University of Kansas, Lawrence, KS

1989-1992
Associate Professor, Department of Microbiology
University of Kansas, Lawrence, KS

1992-1996
Director, Div. of Neurovirology; Associate Professor, Dept. of Microbiology, Immunology and Neurology
University of Miami, Miami, FL

1996-
Lewis Lerh/3M Professor, School of Biological Sciences
University of Nebraska, Lincoln, NE

2000-
Director, Nebraska Center for Virology
University of Nebraska, Lincoln, NE

Honors and Professional Affiliations

Review Panel Member, California University-wide AIDS Research Program
1997-

Member, AIDS and Related Research study session, 1994-1999

Site visit reviewer for Johns Hopkins, (1998, 1999), Princeton (2000)

NCI Intramural program external reviewer (2001), Chair, special review panel (1999, 2001)

Ad Hoc reviewer for USDA
1992-

Ad Hoc reviewer for FDA
1990-

Member of the Kansas University AIDS task force
1990-1992

Scientific advisor to Kansas governor's AIDS task force
1988-1992

Midwestern State University Association lecturer
1989-90

Cora Downs Award for most distinguished undergraduate; Sigma Xi; Phi Beta Kappa