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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Construction of infectious SIV/HIV-2 chimeras
S Ranjbar1, U Bhattacharya, J Oram
1Division of Retrovirology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, UK.
AIDS (London, England)
|January 11, 2000
Summary
Researchers created novel simian-human immunodeficiency virus (SHIV) chimeras by combining SIVmac and HIV-2 genes. These SHIV models successfully replicated in vivo, offering valuable tools for studying HIV-2 vaccine evasion mechanisms.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Live attenuated vaccines against Simian Immunodeficiency Virus (SIV) can be circumvented by Human Immunodeficiency Virus type 2 (HIV-2).
- Understanding the mechanisms of HIV-2 immune evasion is crucial for developing effective vaccines.
Purpose of the Study:
- To construct novel SIV/HIV-2 chimeras (SHIV) capable of in vivo replication.
- To utilize these SHIV as tools for elucidating how HIV-2 bypasses SIV vaccine-induced protection.
Main Methods:
- Construction of SHIV expressing specific HIV-2 genes (vpx, vpr, tat, rev, env or gag, pol) in an SIVmac backbone.
- In vitro replication assessment in cell lines and peripheral blood mononuclear cells (PBMC).
- In vivo infectivity studies in macaques.
Main Results:
- SHIV-2isy env and SHIV-2isy gag/pol stocks were prepared. The 5' and 3' boundaries of the SHIV-2isy gag/pol construct were critical for in vitro infectivity.
- SHIV-2isy env replicated in human and simian PBMC, while SHIV-2isy gag/pol replicated in human PBMC.
- In vivo, SHIV-2isy env was isolated from one of two cynomolgus macaques, SHIV-2isy gag/pol from one of two cynomolgus macaques and both rhesus macaques.
Conclusions:
- This study reports the first SIV/HIV-2 chimeras infectious in macaques.
- This marks the first infectious chimera with replaced SIV gag and pol genes from an HIV isolate.
