Abstract

Animal models for AIDS are needed to study the pathogenesis of disease and to facilitate the development of vaccines and drug therapies. Simian Immunodeficiency Virus (SIV) infection of macaques promises to be a valuable system for such studies. SIV is similar to the human AIDS virus HIV in its biological properties, it is related in sequence to HIV and it induces a disease in monkeys with remarkable parallels to AIDS in man. Results of experiments regarding SIV disease pathogensis and vaccine development could suggest reasonable approaches for human AIDS prevention. In the proposed research, molecular determinants of SIV persistence in vivo will be identified and mechanisms by which the persistent virus carrier state is achieved and maintained will be examined. These goals will be achieved through in vitro and in vivo testing of SIV mutants of defined sequence and through analysis of some of the characteristics of persistent SIV infection. The role of defined mutations on tropism and pathogenicity will be examined. Ongoing attempts to achieve protective immunity through vaccination will be extended.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025328-03
Application #
3138794
Study Section
(SRC)
Project Start
1987-09-01
Project End
1990-11-30
Budget Start
1989-09-01
Budget End
1990-11-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Stansell, Elizabeth; Panico, Maria; Canis, Kevin et al. (2015) Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate. PLoS One 10:e0124784
Postler, Thomas S; Bixby, Jacqueline G; Desrosiers, Ronald C et al. (2014) Systematic analysis of intracellular trafficking motifs located within the cytoplasmic domain of simian immunodeficiency virus glycoprotein gp41. PLoS One 9:e114753
Westmoreland, Susan V; Converse, A Peter; Hrecka, Kasia et al. (2014) SIV vpx is essential for macrophage infection but not for development of AIDS. PLoS One 9:e84463
Postler, Thomas S; Desrosiers, Ronald C (2012) The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-?B activation through TGF-?-activated kinase 1. Cell Host Microbe 11:181-93
Postler, Thomas S; Martinez-Navio, José M; Yuste, Eloísa et al. (2012) Evidence against extracellular exposure of a highly immunogenic region in the C-terminal domain of the simian immunodeficiency virus gp41 transmembrane protein. J Virol 86:1145-57
Martinez-Navio, Jose M; Desrosiers, Ronald C (2012) Neutralizing capacity of monoclonal antibodies that recognize peptide sequences underlying the carbohydrates on gp41 of simian immunodeficiency virus. J Virol 86:12484-93
Stansell, Elizabeth; Canis, Kevin; Haslam, Stuart M et al. (2011) Simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with O-linked carbohydrate. J Virol 85:582-95
Stansell, Elizabeth; Desrosiers, Ronald C (2010) Fundamental difference in the content of high-mannose carbohydrate in the HIV-1 and HIV-2 lineages. J Virol 84:8998-9009
Yuste, Eloisa; Bixby, Jacqueline; Lifson, Jeffrey et al. (2008) Glycosylation of gp41 of simian immunodeficiency virus shields epitopes that can be targets for neutralizing antibodies. J Virol 82:12472-86

Showing the most recent 10 out of 79 publications