Heterogeneity of human immunodeficiency virus type 1 (HIV- 1) has a significant impact on viral fitness, disease progression in the patient, emergence of drug resistance, and development of an effective vaccine. Although encompassing a broad range of topics, all of our research projects are related to HIV-1 genetic diversity.
- We have recently observed that the replicative capacity or fitness of HIV-1 is very strong predictor of disease progression. HIV-1 fitness and diversity appears to increase during disease, which suggests the Red Queen Hypothesis may be in play.
- Several divergent HIV subtypes co-circulate in throughout the world. We now have evidence that subtype C, which dominates the HIV-1 epidemic may actually be less fit. This observation provides evidence for HIV-1 attenuation in the epidemic.
- As part of a program project, we are testing the anti-HIV activity of beta chemokine analogs. This project involves testing these drugs against divergent, primary HIV- 1 strains, isolated throughout the world. We are trying to characterize the mechanism of inhibition by these chemokine analogs by studying HIV-1 binding to CD4 and CCR5. A beta chemokine analog may be employed as vaginal viricide to prevent HIV infections in developing countries.
- Treatment with antiretrovirals results in the emergence of drug resistant HIV- 1 isolates. In many instances, these drug resistant isolates may pre-exist and even predominate in the intrapatient HIV population prior to treatment. We are studying the baseline and emergence of drug resistant HIV- 1 isolates in HIV-infected Ugandans.
Ball, S.C., A. Abraha, K.R. Collins, A.J. Marozsan, M.E. Quiñones-Mateu, A. Penn-Nicholson, M. Murray, N. Richard, M. Lobritz, P. A. Zimmerman, T. Kawamura, A. Blauvelt, and E.J. Arts. 2003. Poor ex vivo fitness of CCR5-tropic subtype C human immunodeficiency virus type 1. J. Virol. 77:[PubMed].
Quiñones-Mateu, M. E., Y. Gao, S.C. Ball, A.J. Marozsan, A. Abraha, and E.J. Arts. 2002. In vitro intersubtype recombinants of human immunodeficiency virus type 1: Comparison to recent and circulating in vivo recombinant forms. J. Virol.76:9600-9613. [PubMed]
Collins, K.R., M.E. Quiñones-Mateu, M. Wu, H. Luzze, J.L. Johnson, C. Hirsch, Z. Toossi, and E. J. Arts. 2002. Human immunodeficiency virus type 1 (HIV-1) quasispecies at the sites of Mycobacterium tuberculosis infection contribute to systemic HIV-1 heterogeneity. J. Virol. 76: 1697-1709. [PubMed]
Quiñones-Mateu, M.E. and E.J. Arts. 2001. HIV-1 Fitness: Implications for Drug Resistance, Disease Progression, and Global Epidemic Evolution. pp. 134-170 in HIV Sequence Compendium 2001. [link]
Marozsan, A.J., V. Torre, M. Johnson, S.C. Ball, J.V. Cross, D.J. Templeton, M.E. Quinones-Mateu, R.E. Offord, and E.J. Arts. 2001. Mechanisms involved in stimulation of human immunodeficiency virus type 1 replication by aminooxypentane RANTES. J. Virol. 75: 8624-8638. [PubMed]