The primary goal of this research is to use EIAV as a natural biological model of persistent infections to examine the molecular mechanisms of viral gene expression which correlate with latency and disease in the infected host. There are three specific aims. First, the investigator proposes to characterize the temporal patterns of provirus integration and viral transcription during persistent and cytopathic infections in vitro. The second is to try to characterize the patterns of provirus integration and viral gene expression during stages of latency and disease in experimentally infected ponies. The third is to attempt to utilize infectious molecular clones of EIAV to identify and characterize viral determinants important in regulating virus replication, virulence and host pathogenesis. In the first two objectives, DNA and RNA polymerase chain reaction (PCR) will be used to define the patterns of provirus integration and viral transcription in persistently- and cytopathically-infected equine cells and from tissues of experimentally infected ponies during stages of acute, chronic and inapparent disease. The third objective will use infectious molecular clones of EIAV in mutagenesis studies to identify viral genes and cis-regulatory sequences essential for virus replication and virulence in horses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA049296-08
Application #
2007754
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1997-03-01
Project End
2000-12-31
Budget Start
1997-03-01
Budget End
1997-12-31
Support Year
8
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Genetics
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zhang, Baoshan; Montelaro, Ronald C (2009) Replication of equine infectious anemia virus in engineered mouse NIH 3T3 cells. J Virol 83:2034-7
Jin, Jing; Sturgeon, Timothy; Weisz, Ora A et al. (2009) HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking. PLoS One 4:e6551
Sun, Chengqun; Zhang, Baoshan; Jin, Jing et al. (2008) Binding of equine infectious anemia virus to the equine lentivirus receptor-1 is mediated by complex discontinuous sequences in the viral envelope gp90 protein. J Gen Virol 89:2011-9
Zhang, Baoshan; Sun, Chengqun; Jin, Sha et al. (2008) Mapping of equine lentivirus receptor 1 residues critical for equine infectious anemia virus envelope binding. J Virol 82:1204-13
Jin, Jing; Sturgeon, Timothy; Chen, Chaoping et al. (2007) Distinct intracellular trafficking of equine infectious anemia virus and human immunodeficiency virus type 1 Gag during viral assembly and budding revealed by bimolecular fluorescence complementation assays. J Virol 81:11226-35
Chen, Chaoping; Jin, Jing; Rubin, Marc et al. (2007) Association of gag multimers with filamentous actin during equine infectious anemia virus assembly. Curr HIV Res 5:315-23
Zhang, Baoshan; Jin, Sha; Jin, Jing et al. (2005) A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus. Proc Natl Acad Sci U S A 102:9918-23
Chen, Chaoping; Vincent, Olivier; Jin, Jing et al. (2005) Functions of early (AP-2) and late (AIP1/ALIX) endocytic proteins in equine infectious anemia virus budding. J Biol Chem 280:40474-80
Jin, Sha; Chen, Chaoping; Montelaro, Ronald C (2005) Equine infectious anemia virus Gag p9 function in early steps of virus infection and provirus production. J Virol 79:8793-801
Jin, Sha; Zhang, Baoshan; Weisz, Ora A et al. (2005) Receptor-mediated entry by equine infectious anemia virus utilizes a pH-dependent endocytic pathway. J Virol 79:14489-97

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