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 (KS). One of laboratory’s largest ongoing collaborative research projects – which has been ongoing for the past 20 years – involves multiple U.S. research institutions and the University of Zambia, School of Medicine to study HIV/AIDS, and Kaposi’s sarcoma associated human herpesvirus (KSHV) transmission, disease pathogenesis, treatment, and prevention. More recently the study on HIV and KS has been expanded to Tanzania. Dr. Wood has built research laboratories and research teams in these two African countries to conduct HIV and related malignancies research, and has frequent exchanges of students and fellows with these two study sites.
The Wood laboratory has been involved in the molecular biology of HIV and a human herpesvirus associated with KS named KSHV which has been linked to KS, an AIDS defining cancer. The laboratory has been interested in the route of KSHV transmission and whether infection by this virus can directly lead to KS is not clear. 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) the genotypes of the circulating virus in Africa, (3) to determine whether vertical transmission can occur and the source of vertical and/or horizontal transmission, (4) the rate of transmission and whether treatment with anti-HIV regimens to restore the immune system can prevent transmission, and (5) where are the potential viral reservoirs in infected individuals.
One of the laboratory’s findings is that there is a high prevalence of HIV infection in Zambia’s normal female population and 40% of the population 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 found that vertical transmission can occur but the frequency is not high. Most of the transmission occur post-delivery during early childhood, the source of transmission is via saliva contact from both within and outside the household, and HIV is a major co-factor for transmission. The lab has recently found that the central nervous system (CNS) is a site of latency for KSHV, and neuronal cells in patients can be infected. Ongoing studies now focus on the effect of KSHV on the CNS, and its effects on HIV neuropathogenesis.
Currently the laboratory is studying factors that contribute to the development of KS in KSHV infected individuals as well as their immune response against KSHV, and whether there are any differences between patients with HIV associated epidemic KS versus those with endemic KS without HIV. The approaches being taken are to analyze both the innate and cell mediated immune response, as well as tumor transcriptome analysis of the two types of KS to identify biomarkers or alternation in both viral and cellular genes that could lead to KS.
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.
Selected Recent Publications
- Tso FY, Lidenge SJ, Peña PB, Clegg AA, Ngowi JR, Mwaiselage J, Ngalamika O, Julius P, West JT, Wood C. 2020. High prevalence of pre-existing serological cross-reactivity against SARS-CoV-2 in sub-Sahara Africa. Int J Infect Dis. 2021, 102:577-583. Nov 8:S1201-9712(20)32310-9. doi: 10.1016/j.ijid.2020.10.104. PMID: 33176202.
- Ngalamika O, Tso FY, Lidenge SJ, Munsaka S, Shea D, Wood C and West TJ. 2020. Outcome Markers of ART-Treated HIV+ Patients with Early Stage Kaposi’s Sarcoma. PloS One. Jul 7;15(7):e0235865. doi: 10.1371/journal.pone.0235865. PMID: 32634155; PMCID: PMC7340279.
- Poppe L, Wood C, and West J. 2020. The presence of Antibody-Dependent Cell Cytotoxicity-Mediating Antibodies in Kaposi Sarcoma-Associated Herpesvirus-Seropositive individuals does not correlate with disease pathogenesis or progression. J Immunol.. Sep 30;ji2000489. doi: 10.4049/jimmunol.2000489. Epub ahead of print. PMID: 32998986.
- Bennett SJ, Chunda-Liyoka C, Poppe LK, Meinders K, Chileshe C, West JT and Wood C. 2020 High NNRTI resistance levels in HIV-1 infected Zambian mother-infant pairs. AIDS. Jul 23. doi: 10.1097/QAD.0000000000002614. Online ahead of print. PMID: 32732629.
- Poppe LK, Kankasa C, Wood C and West J. 2020. Relationships between maternal antibody responses and early childhood infection with Kaposi Sarcoma-Associated Herpesvirus. J Infect Dis. Oct 13;222(10):1723-1730. doi: 10.1093/infdis/jiaa288. PMID: 32459337.
- Lidenge SJ, Kossenkov AV, Tso FY, Wickramasinghe J, Privatt SR, Ngalamika O, Ngowi JR, Mwaiselage J, Lieberman PM, West JT, and Wood C. 2020. Comparative Transcriptome Analysis of Endemic and Epidemic Kaposi’s Sarcoma (KS) Lesions and the Secondary Role of HIV-1 in KS Pathogenesis. PLoS Pathog. Jul 24;16(7):e1008681. doi: 10.1371/journal.ppat.1008681. eCollection PMID: 32706839; PMCID: PMC7406108
- Lidenge SJ, Tso FY, Mortazavi,Y, Mortazavi Y, Ngowi JR, Shea DM, Mwaiselage J, Wood C, and West JT. 2020. Viral and Immunological Analytes Are Poor Predictors of the Clinical Treatment Response in Kaposi’s sarcoma Patients. Jun 16;12(6):1594. doi: 10.3390/cancers12061594. PMID: 32560243; PMCID: PMC7352224
- Lidenge SJ, Tso FY, Ngalamika O, Kolape J, Ngowi JR, Mwaiselage J, Wood C, and West JT. 2020. Lack of CD8+ T-cell co-localization with Kaposi’s sarcoma-associated herpesvirus infected cells in Kaposi’s sarcoma tumors. Oncotarget. Apr 28;11(17):1556-1572. doi: 10.18632/oncotarget.27569. PMID: 32391124; PMCID: PMC7197452.
- Lidgenge SJ, Tran T, Tso FY, Ngowi JR, Shea DM, Mwaiselage J, Wood C, West JT. 2020. Prevalence of Kaposi's Sarcoma-associated Herpesvirus and Transfusion-transmissible Infections in Tanzanian Blood Donors. Int J Infect Dis. Jun;95:204-209. doi: 10.1016/j.ijid.2020.04.018. PMID: 32294540
- Mortazavi Y, Lidenge SJ, Tran T, West JT, Wood C and Tso FY. 2020. The Kaposi’s Sarcoma-associated Herpesvirus (KSHV) gH/gL Complex is the Predominant Neutralizing Antigenic Determinant in KSHV-Infected Individuals. Viruses. Feb 26;12(3):256. doi: 10.3390/v12030256. PMID: 32111001; PMCID: PMC7150787.
- Kwon EH, Musema GMA, Boelter J, Townsend S, Tshala-Katumbay D, Kayembe PK, West J, and Wood C. 2020. HIV-1 Subtypes and Drug Resistance Mutations among Female Sex Workers Varied in Different Cities and Regions of the Democratic Republic of Congo. PLoS One. Feb 11;15(2):e0228670. doi: 10.1371/journal.pone.0228670. PMID: 32045455; PMCID: PMC7012409.
- Klein C, Kahesa C, Mwaiselage J, West J, Wood C, and Angeletti PC. 2020. How the Cervical Microbiota Contributes to Cervical Cancer Risk in Sub-Saharan Africa. Front Cellular Infect Microbiol. Feb 12;10:23. doi: 10.3389/fcimb.2020.00023. PMID: 32117800; PMCID: PMC7028704.
- Chunda-Liyoka C; Lubeya MK, Imakando M, Kisling S, Majid S, Willis MS, Wood C, Kankasa C and DiRusso CC. 2020. Healthy Pregnancies and Essential Fats: Focus Group Discussions with Zambian Women on Dietary Need and Acceptability of a Novel RUSF Containing Fish Oil DHA. BMC Pregnancy Childbirth. Feb 10;20(1):93. doi: 10.1186/s12884-020-2783-8. PMID: 32041569; PMCID: PMC7011535.