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My laboratory focuses on the use of human immunodeficiency virus (HIV) vectors for gene therapeutics and to study HIV itself. Murine leukemia virus, optimized as a vector and widely used, cannot infect mitotically inactive cells. HIV, however, has multiple proteins that allow infection of nondividing cells. I have been able to demonstrate very efficient gene transfer into human hematopoietic stem cells (HSC) using HIV vectors. We have constructed vectors with a variety of anti-HIV genes and are now determining their efficacy in both established cell lines and primary cells. We are also characterizing HSC subsets (a potential target of these vectors), transducing those cells with vectors encoding genes that could influence differentiation pathways, both in vitro and in the NOD/SCID mouse.

At present there is no small animal model for HIV. In the mouse there appears to be a block in viral replication at the level of assembly/release. We have begun several genetic screens to characterize such a factor(s) and have narrowed it down to a single autosome. Isolation of the gene(s) responsible should facilitate production of transgenic animals for pathogenesis and vaccine studies.

HIV replication is very error-prone, and conventional wisdom suggests that the high mutation rate is directly related to the fidelity of the viral enzyme reverse transcriptase (RT). We have established a genetic reversion assay and shown that RT of several different retroviruses has the same error rate as that of HIV. We are now attempting to determine whether the measured error rate reflects that of RT or RNA polymerase II, the other, oft-forgotten polymerase involved in HIV replication. This has implications for drug resistance, immune evasion, and vaccine strategies against the virus.

Recent Publications (PubMed)

Baliga CS, van Maanen M, Chastain M, Sutton RE. 
Vaccination of Mice with Replication-Defective Human Immunodeficiency Virus Induces Cellular and Humoral Immunity and Protects against Vaccinia Virus-gag Challenge. Mol Ther. 2006 May 18

Coskun AK, van Maanen M, Nguyen V, Sutton RE. 
Human chromosome 2 carries a gene required for production of infectious human immunodeficiency virus type 1.
J Virol. 2006 Apr;80(7):3406-15.
 
Laakso MM, Sutton RE. 
Replicative fidelity of lentiviral vectors produced by transient transfection.
Virology. 2006 May 10;348(2):406-17. Epub 2006 Feb 8.
 
Coskun AK, Sutton RE. 
 Expression of glucose transporter 1 confers susceptibility to human T-cell leukemia virus envelope-mediated fusion.
J Virol. 2005 Apr;79(7):4150-8.
 
Conklin LD, McAninch RE, Schulz D, Kaluza GL, LeMaire SA, Coselli JS, Raizner AE, Sutton RE. 
 HIV-based vectors and angiogenesis following rabbit hindlimb ischemia.
J Surg Res. 2005 Jan;123(1):55-66.