Abstract

We study HIV and SIV variants that have the Rev/RRE regulatory system replaced by CTE with the goal to evaluate their pathogenicity. Attenuated virus strains have been shown to be effective in protecting against virus challenge, but the strains studied so far have also been shown to be associated with pathogenicity. We found that the SIV variant virus can persistently infect rhesus macaques (von Gegerfelt A, et al: J Virol 73:6159-65, 1999). Therefore, the replacement of the essential Rev regulation by the CTE generated a virus variant that retained its replicative capacity both in vitro and in vivo, albeit at low levels. Infection of neonate and juvenile macaques by the Rev-independent SIV strains did not induce any signs of immune disfunction or disease during the 1-3 years of follow-up. These data demonstrate that Rev/RRE regulatory mechanism is required for high levels of virus propagation and that this control mechanism plays an important role in the pathogenicity of SIV. The replacement of Rev/RRE by the hTAP/CTE system provides a novel approach to lower the virulence of a pathogenic lentivirus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010350-01
Application #
6422521
Study Section
(LGD)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Bergamaschi, Cristina; Jalah, Rashmi; Kulkarni, Viraj et al. (2009) Secretion and biological activity of short signal peptide IL-15 is chaperoned by IL-15 receptor alpha in vivo. J Immunol 183:3064-72
Robinson, T M; Sidhu, M K; Pavlakis, G N et al. (2007) Macaques co-immunized with SIVgag/pol-HIVenv and IL-12 plasmid have increased cellular responses. J Med Primatol 36:276-84
von Gegerfelt, Agneta S; Rosati, Margherita; Alicea, Candido et al. (2007) Long-lasting decrease in viremia in macaques chronically infected with simian immunodeficiency virus SIVmac251 after therapeutic DNA immunization. J Virol 81:1972-9
Kumar, Sanjeev; Yan, Jian; Muthumani, Karuppiah et al. (2006) Immunogenicity testing of a novel engineered HIV-1 envelope gp140 DNA vaccine construct. DNA Cell Biol 25:383-92
von Gegerfelt, Agneta S; Alicea, Candido; Valentin, Antonio et al. (2006) Long lasting control and lack of pathogenicity of the attenuated Rev-independent SIV in rhesus macaques. AIDS Res Hum Retroviruses 22:516-28
Egan, Michael A; Megati, Shakuntala; Roopchand, Vidia et al. (2006) Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice. Vaccine 24:4510-23
Hel, Zdenek; Tsai, Wen-Po; Tryniszewska, Elzbieta et al. (2006) Improved vaccine protection from simian AIDS by the addition of nonstructural simian immunodeficiency virus genes. J Immunol 176:85-96
Schadeck, Eva B; Sidhu, Maninder; Egan, Michael A et al. (2006) A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques. Vaccine 24:4677-87
Kutzler, Michele A; Robinson, Tara M; Chattergoon, Michael A et al. (2005) Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 175:112-23
Rosati, Margherita; von Gegerfelt, Agneta; Roth, Patricia et al. (2005) DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge. J Virol 79:8480-92

Showing the most recent 10 out of 12 publications