Phyllis J. Kanki, D.V.M., S.D.

Associate Professor of Pathobiology
Department of Immunology & Infectious Diseases
Harvard School of Public Health
651 Huntington Avenue, FXB 405
Boston, MA 02115
Tel: 617-432-1267
Fax: 617-739-8348
e-mail: pkanki@hsph.harvard.edu

In 1985, we provided the first evidence of a retrovirus in West African people more closely related to Simian Immunodeficiency Virus (SIV) than to HIV-1, the prototype AIDS virus. Human immunodeficiency Virus type 2 (HIV-2), as this virus is now called, shares many virologic properties with HIV-1, including cell tropism, antigenic and genetic similarities and genome organizations. Our epidemiologic studies of both viruses in Africa, indicate a curious geographic distribution of these two related viruses, HIV-2 appears at high rates in West Africa, where the HIV-1 epidemic is now spreading.

Despite early fears that HIV-2 would create a second AIDS pandemic, current information suggests that HIV-2 and HIV-1 may have distinct biologic properties in people. It is therefore relevant to assess these differences in populations infected with significant rates of both HIV-2 and HIV-1. Senegal is a country with such populations and the collaboration we have had for the past ten years provides a strong base for continued research.

We are involved in a number of prospective studies of HIV-2 and HIV-1 infected people in Senegal. By following healthy HIV-positive individuals over time, we have found that the rate of AIDS development is >10-fold higher in HIV-1 infected individuals compared to HIV-2. We have found that HIV-2 is less transmissible compared to HIV-1, by both perinatal and heterosexual routes. Thus, HIV-2 appears to be a less virulent HIV virus, and we addressed the hypothesis that it might provide protection from subsequent HIV-1 infection. Our recent study shows that this appears to be the case, with close to 70% protection conferred by HIV-2 infection. Evaluation of other sexually transmitted diseases in these prospectively followed women demonstrated that high risk behavior was not a reason for the decreased rate of HIV-1 infection in our HIV-2 seropositive women.

Laboratory studies seek to explore viral mechanisms for the differences in observed biology between HIV-2 and HIV-1. Inter- and intra-patient variation in the nucleotide sequence of the envelope gene is thought to play a role in the pathogenesis of HIV-1. We have studied the intra-patient variation of a portion of the HIV-2 envelope gene to determine if this is similar to HIV-1. Overall intra-patient variation in HIV-2 appears to be less than that of HIV-1 and variation does correlate with clinical evidence of immunosuppression or overt disease. Similarly, we have utilized quantitative PCR to determine proviral titers of sequentially evaluated HIV-infected individuals. The range of HIV-2 proviral titer is 10 to 100-fold lower than that of HIV-1, suggesting that decreased pathogenicity may be due in part to a lower viral burden.

Selected Publications

Kanki P., Hamel D.J., Sankalé J.L., Hsieh C.C., Thior I., Barin F., Woodcock, S.A., Gueye-NDiaye, A., Zhang, E., Montano, M., Siby, T., Marlink R., Ndoye, I., Essex, M., and MBoup, S. HIV-1 Subtypes Differ in Disease progression J. Infect. Dis. 1999;179: 68-73.

Dieng-Sarr A., Hamel D.J., Thior I. Kokkotou E., Sankalé J.L., Marlink R.G., Coll-Seck E.M., Essex M. E., Siby T., NDoye I., MBoup S., and Kanki P. HIV-1 and HIV-2 Dual Infection: Lack of HIV-2 provirus correlates with low CD4+ lymphocyte counts. AIDS 1998;12:131-7.

Kanki, P., Epidemiology and Natural History of HIV-2, in AIDS: Etiology, Diagnosis, Treatment and Prevention, V. DeVita, S. Hellman, and S. Rosenberg, Editors. J. B. Lippincott Co.: Philadelphia. p. 97-108 (1996).

Kanki, P., Eisen, G., Travers, K.U., Marlink, R.G., Essex M.E., Hsieh C.C., and MBoup S. HIV-2 and Natural Protection against HIV-1 infection. (Technical Comment) Science 1996; 272:1959-60.

Sankalé, J.L., R. Sallier de la Tour, R.G. Marlink, R. Scheib, S. MBoup, M.E. Essex, and P. Kanki. Distinct quasi-species in the blood and the brain of an HIV-2 infected individual. Virology 1996;226:418-23.

Travers K, Mboup S, Marlink R, Gueye-Ndiaye A, Siby T, Thior I, Traoré I, Dieng-Sarr A, Sankalé J-L, Mullins C, NDoye I, Hsieh C-C, Essex M, and Kanki P. Natural protection against HIV-1 infection provided by HIV-2. Science 1995;268:1612-15.

Essex M, Mboup S, Kanki P, and Kalengayi M, eds.AIDS In Africa, New York: Raven Press, 1994.

Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, Traoré I, Hsieh C-C, Dia MC, Gueye EH, Hellinger J, Gueye-Ndiaye A, Sankalé J-L, NDoye I, Mboup S, and Essex M. Reduced rate of disease development with HIV-2 compared to HIV-1. Science 1994;265:1587-1590.

Kanki P, Mboup S, Marlink R, Travers K, Hsieh C-C, Gueye A, Boye C, Sankalé J-L, Donnelly C, Leisenring W, Siby T, Thior I, Dia M, Gueye E-H, NDoye I, and Essex M. Prevalence and risk determinants of Human Immunodeficiency Virus Type 2 (HIV-2) and Human Immunodeficiency Virus Type 1 (HIV-1) in West African female prostitutes. Amer J Epidemiol 1992;136:895-907.

Barin F, Mboup S, Denis F, Kanki P, Allan JS, Lee T-H, and Essex M. Serological evidence for virus related to Simian T-Lymphotropic Retrovirus III in residents of West Africa. Lancet 1985, II:1387-90.