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Tebit, Denis

Denis Tebit

Primary Appointment

Microbiology, Immunology, and Cancer Biology

Contact Information

Jordan Hall, Room 7088
Charlottesville, VA 22903
Telephone: 924-1808
Email: dmt6u@virginia.edu

Research Interests

HIV diversity, evolution, fitness, drug resistance and disease progression

Research Description

Human immunodeficiency viruses (HIV) crossed the species barrier from non-human primates multiple times in Central Africa leading to the establishment of two distinct HIV types (HIV-1 and HIV- 2) which are further sub-classified into groups (HIV-1: groups M, N, O and P and HIV-2 groups A and B). Group M dominates the epidemic with 9 subtypes and about 55 circulating recombinant forms (CRF). The low prevalence and poor establishment of groups N, O, P as well as HIV-2 may be attributable to viral factors such as poor transmissibility and fitness or host restriction factors including HLA types. The role of this divergent evolution in the development of drug resistance, fitness and disease progression among HIV and SIV strains remains largely unknown. Despite the abundance of studies on the pattern of drug resistance and disease progression in HIV-1 subtype B patients, there is a paucity of similar data on HIV genotypes circulating in sub-Saharan Africa where the epidemic is hitting the hardest. Such studies are of particular importance at a time when the roll out of Highly Active Antiretroviral Therapy (HAART) in sub-Saharan Africa is gradually making a difference. Through collaboration with Dr. Pascal Bessong at the University of Venda (Univen), Thohoyandou, in the Limpopo Province of Northern South Africa, we have established contacts with HIV clinics throughout the Province that have been administering HAART since 2004. Studies include the establishment of electronic databases that would facilitate treatment follow-up and outcome studies, utilizing novel genotypic and phenotypic assays to determine reasons for HAART failure and the pattern of drug resistance development especially in subtype C. These studies are performed on site at the University of Venda and also in our UVa laboratories and involve joint collaboration of Faculty, Staff and students from both Universities. At our UVa laboratory, we continue to study by in vitro mutagenesis experiments how the divergent evolution of HIV group O has affected resistance to novel antiretrovirals. We are also expanding on earlier studies of drug resistance development to include aspects of fitness and disease progression in CRF02_AG and CRF06cpx strains, the most prevalent recombinant HIVs in West and Central Africa. Using recent molecular Bayesian analyses methods coupled with our phenotypic analyses, old and recent sequences from the HIV database will be used to reconstruct the dissemination dynamics of CRF02_AG and CRF06cpx strains in West and Central Africa during the last 2 decades.

Selected Publications

Liu Y, Rao U, McClure J, Konopa P, Manocheewa S, Kim M, Chen L, Troyer RM, Tebit DM, Holte S, Arts EJ, Mullins JI, Impact of mutations in highly conserved amino acids of the HIV-1 Gag-p24 and Env-gp120 proteins on viral replication in different genetic backgrounds., 2014; PloS one. 9(4) e94240 PMID: 24713822 | PMCID: PMC3979772

Kyeyune F, Nankya I, Metha S, Akao J, Ndashimye E, Tebit DM, Rodriguez B, Kityo C, Salata RA, Mugyenyi P, Arts E, Treatment failure and drug resistance is more frequent in HIV-1 subtype D versus subtype A-infected Ugandans over a 10-year study period., 2013; AIDS (London, England). 27(12) 1899-909 PMID: 23727942 |

Tebit DM, Ndembi N, Weinberg A, Qui?ones-Mateu ME, Mucosal transmission of human immunodeficiency virus., 2012; Current HIV research. 10(1) 3-8 PMID: 22264040 | PMCID: PMC3744389

Santos AF, Tebit DM, Lalonde MS, Abecasis AB, Ratcliff A, Camacho RJ, Diaz RS, Herchenr?der O, Soares MA, Arts EJ, Effect of natural polymorphisms in the HIV-1 CRF02_AG protease on protease inhibitor hypersusceptibility., 2012; Antimicrobial agents and chemotherapy. 56(5) 2719-25 PMID: 22330918 | PMCID: PMC3346603

Tebit DM, Lobritz M, Lalonde M, Immonen T, Singh K, Sarafianos S, Herchenr?der O, Kr?usslich HG, Arts EJ, Divergent evolution in reverse transcriptase (RT) of HIV-1 group O and M lineages: impact on structure, fitness, and sensitivity to nonnucleoside RT inhibitors., 2010; Journal of virology. 84(19) 9817-30 PMID: 20631150 | PMCID: PMC2937803

B?hler T, Mrosek V, M?ller K, Schnitzler P, Hartmann M, Ouedraogo T, Coulibaly B, Si? A, Bartonova V, Tebit DM, Kr?usslich HG, Cross-clade recognition of HIV-1 CAp24 by CD4+ T cells in HIV-1-infected individuals in Burkina Faso and Germany., 2009; The open AIDS journal. 3() 4-7 PMID: 19554213 | PMCID: PMC2701271

Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, Tebit DM, Zhao H, Avila S, Lobritz MA, McElrath MJ, Le Gall S, Mullins JI, Arts EJ, Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response., 2009; PLoS pathogens. 5(4) e1000365 PMID: 19343217 | PMCID: PMC2659432

Abraha A, Nankya IL, Gibson R, Demers K, Tebit DM, Johnston E, Katzenstein D, Siddiqui A, Herrera C, Fischetti L, Shattock RJ, Arts EJ, CCR5- and CXCR4-tropic subtype C human immunodeficiency virus type 1 isolates have a lower level of pathogenic fitness than other dominant group M subtypes: implications for the epidemic., 2009; Journal of virology. 83(11) 5592-605 PMID: 19297481 | PMCID: PMC2681953

Tebit DM, Sangar? L, Makamtse A, Yameogo S, Somlare H, Bado G, Kouldiaty BG, Sathiandee K, Tiba F, Sanou I, Ou?draogo-Traor? R, Zoungrana L, Diallo I, Drabo JY, Kr?usslich HG, HIV drug resistance pattern among HAART-exposed patients with suboptimal virological response in Ouagadougou, Burkina Faso., 2008; Journal of acquired immune deficiency syndromes (1999). 49(1) 17-25 PMID: 18667925 |

Liu Y, McNevin J, Zhao H, Tebit DM, Troyer RM, McSweyn M, Ghosh AK, Shriner D, Arts EJ, McElrath MJ, Mullins JI, Evolution of human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitopes: fitness-balanced escape., 2007; Journal of virology. 81(22) 12179-88 PMID: 17728222 | PMCID: PMC2169017

Klose N, Coulibaly B, Tebit DM, Nauwelaers F, Spengler HP, Kynast-Wolf G, Kouyat? B, Kr?usslich HG, B?hler T, Immunohematological reference values for healthy adults in Burkina Faso., 2007; Clinical and vaccine immunology : CVI. 14(6) 782-4 PMID: 17442846 | PMCID: PMC1951086