Harvard Medical School

Contact Information:

New England Regional Primate Research Center

P.O. Box 9102

Southborough, MA 01772-9102

phone: 508-624-8040

fax: 508-624-8190

 

ronald_desrosiers@hms.harvard.edu

 

Research Summary

The Desrosiers laboratory studies mechanisms of viral pathogenesis using monkey models of human disease.

The viruses that cause AIDS in humans, HIV-1 and HIV-2, are members of the lentivirus subfamily of retroviruses. The simian immunodeficiency viruses (SIVs) are nonhuman primate lentiviruses that are the closest known relatives of the HIVs. They closely parallel their human counterparts in genomic organization, gene sequence and biological properties. They are being used to study the molecular determinants of AIDS pathogenesis. By what mechanisms are SIV and HIV able to evade ongoing immune responses? Why are HIV and SIV so resistant to antibody-mediated neutralization? What is the role of envelope sequence variation? Are the so-called "non-essential" genes essential for persistence and/or pathogenic potential? What are their functional roles? What is the significance of macrophage tropism for disease manifestations? How can we use a better understanding of pathogenesis to make an effective vaccine for AIDS?

A new herpesvirus has been isolated in rhesus monkeys that is a close relative of the human Kaposi sarcoma-associated herpesvirus (KSHV). The contribution of individual genes to disease is being studied.

Selected Publications

Johnson WE, Morgan J, Reitter J, Puffer BA, Czajak S, Doms RW, Desrosiers RC. A REplication-competent, neutralizing sensitive variant of SIV lacking 100 amino acids of envelope. J. Virol. 2002 Mar;76(5): 2075-2086.

Evans DT, Tillman KC, Desrosiers RC. Envelope glycoprotein cytoplasmic domains from diverse lentiviruses interact with the prenylated Rab acceptor. J Virol. 2002 Jan;76(1):327-37.

Johnson WE, Sauvron JM, Desrosiers RC. Conserved, N-linked carbohydrates of human immunodeficiency virus type 1 gp41 are largely dispensable for viral replication. J Virol. 2001 Dec;75(23):11426-36.

Alexander L, Weiskopf E, Greenough TC, Gaddis NC, Auerbach MR, Malim MH, O'Brien SJ, Walker BD, Sullivan JL, Desrosiers RC. Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. J Virol. 2000 May;74(9):4361-76.

Desrosiers RC. Strategies used by HIV that allow persistent viral replication. Nature Med. 1999 Jul;5(7):723-725.