Peter Southern, PhD

Human Retrovirus Transmission and Pathogenesis

I am interested in the cellular and molecular mechanisms underlying virus transmission and the initiation of virus-induced diseases. After working for many years with experimental infections of mice with an RNA virus, lymphocytic choriomeningitis virus (LCMV), my research focus has shifted recently to the study of infections with the human retroviruses, human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus types I and II (HTLV-I and HTLV-II). These retroviruses can be transmitted either vertically or horizontally in human populations and we are beginning to define essential parameters, in both the donor and recipient of infectivity, that impact on the overall probability of transmission. Our experiments are based on primary human cell populations, human organ cultures, and body fluids from seropositive patients. Our goal is to develop manipulable experimental systems that duplicate the natural routes for virus transmission. More specifically, we are investigating the nature of HIV-1 infections in male reproductive tissue to understand variability in the shedding of HIV-1 infectivity in seminal fluid. In recipients, we are interested in defining the mechanisms whereby HIV-1 infectivity can breach epithelial barriers at mucosal surfaces and gain access to intraepithelial leukocytes for the initiation and expansion of primary infections. New insight into HIV transmission, with both cell-free and cell-associated HIV infectivity, will be invaluable in refining vaccine studies and may contribute significantly to the design of novel therapeutic agents to reduce the probability of HIV transmission.

• Maher, D., X. Wu, T. Schacker, J. Horbul, and P. Southern. (2005) HIV binding, penetration, and primary infection in human cervicovaginal tissue. Proc. Natl. Acad. Sci. USA 102: 11504-11509.
• Maher, D., Z-Z. Zhang, T. Schacker, and P. Southern. (2005) Ex vivo modeling of oral HIV transmission in human palatine tonsil. J. Histochem. & Cytochem. 53: 631-642.
• Maher, D., X. Wu, T. Schacker, M. Larson, and P. Southern. (2004) A model system of oral HIV exposure utilizing human palatine tonsil reveals extensive binding of HIV infectivity with limited progression to primary infection. J. Infect. Dis. 190: 1989-1997.
• Meyer, B.J., J-C. de la Torre, and P.J. Southern, (2001) Arenaviruses: genomic RNAs, transcription and replication. Curr. Top. Microbiol. Immunol.
• Chang, S-l, G.W. Griesgraber, P.J. Southern, and C.R. Wagner (2001) Amino acid phosphoramidate monoesters of 3'-azido-3'deoxythymidine: relationship between antiviral potency and intracellular metabolism. J. Med. Chem. 44:223-231.
• Louiero, P., S.O. Southern, P.J. Southern, and M.S. Pombo-de-Oliveira. (2000) Clinicopathological studies of a patient with adult T-cell leukemia and pseudogynecomasty. Am. J. Hematol. 65:256-259.
• LeVasseur, R.J., S.O. Southern, and P.J. Southern. (1998) Mammary epithelial cells support and transfer productive human t-cell lymphotropic virus infections. J. Human Virol. 1:214-233.
• Southern, S.O., and P.J. Southern. (1998) Persistent HTLV-I infection of breast luminal epithelial cells: a role in HTLV transmission. Virology 241:200-214.