Charles Wood
Charles Wood
Lewis Lehr/3M University Professor
Director, Nebraska Center for Virology

Ph.D. Columbia University, 1981
Contact Information
102C Morrison Center
402.472.4550
 

Nebraska Center for Virology 

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 or human herpesvirus-8.

Currently, according to the UNAIDS, there are over 33 million living with HIV, with the majority of the infected individuals living in sub-Saharan Africa. There are still millions of deaths and over 2.5 million cases of new infections are occurring each year. In addition, mother-to-child transmission (MTCT) of HIV-1 remains a significant problem in the resource-constrained settings where the implementation of effective preventive and therapeutic strategies is still not widely available. In the absence of antiretroviral treatment, 30-45% of infants born to HIV-positive mothers have become infected. Globally HIV-1 infected children account for 20% of all HIV-1 related deaths and more than 90% of the infected children under the age of 15 are living in sub-Saharan Africa. Because of the genetic variability of the virus, there are many strains or subtypes of HIV which are found in different regions of the world. For example, in Africa, the HIV-1 subtype C is the most prevalent and account for more than 60% of infections. HIV-1 Subtype C is now the most abundant and the most rapidly expanding subtype in the world. Given the high prevalence of HIV-1 subtype C infections, a better understanding of virus transmission is of significant importance, which is a major focus of our laboratory.

The laboratory has a longstanding research and training program in collaboration with the University of Zambia, in Zambia, a central African nation that lies in the heart of the AIDS epidemic. We found that almost all Zambian HIV are of subgroup C and are rapidly spreading in Zambia. Unfortunately, very little is known about the events that affect mother to child transmission of this subgroup of viruses, regarding the host and viral factors that may affect transmission, and the viral biological properties, pathogenesis, and genetic evolution in infected individuals. The laboratory has been identifying and following HIV infected mother infant pairs from birth onwards, characterizing a panel of subtype C HIV isolated from infected infants at various time points after infection. First to determine virological and host factors that may affect transmission, and then determine factors that may affect disease progression and viral pathogenesis, including the natural evolution of these viruses, in order 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 also underway to the extent of HIV associated neurological diseases in Zambia and factors that can contribute to these HIV associated diseases. We have found that HIV associated neurocognitive disorders (HAND) were present in 22% of the sample population, and the effect and extent of HAND are currently being investigated. This is being carried out by collecting a bank of HIV infected brain specimens, and analyzing for HIV and other opportunistic infections.

The second human virus which is being studied in the laboratory is the KSHV. This virus 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. The ongoing study involves the recruitment and follow-up of mother/infant pairs to determine (1) the seroprevalence for HIV and KSHV, (2) whether KSHV DNA can be found in infants' blood, (3) to determine the source of vertical and/or horizontal transmission, and (4) to determine the effect of anti-retroviral in blocking KSHV 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, and found that early childhood infection by KSHV is very prevalent, it reached adult level by five years of age, and HIV is a co-factor for transmission. Our results also suggest that both vertical and horizontal transmission is possible. The route of transmission is likely to be through saliva and not via breast milk. These findings now enable us to develop strategies for behavioral intervention to prevent KSHV infection in endemic region like sub-Saharan Africa. The risks factors and the source of KSHV that are associated with transmission are currently being determined. Whether infected children will develop KS, and what other co-factors involved in KS are also being investigated.

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


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, 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.