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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
Simian immunodeficiency viruses of diverse origin can use CXCR4 as a coreceptor for entry into human cells
S M Owen1, S Masciotra, F Novembre
1HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Abstract:
Primary simian immunodeficiency virus (SIV) isolated from sooty mangabey (SIVsm [n = 6]), stumptail (SIVstm [n = 1]), mandrill (SIVmnd [n = 1]), and African green (SIVagm [n = 1]) primates were examined for their ability to infect human cells and for their coreceptor requirements. All isolates infected human peripheral blood mononuclear cells (PBMCs) from a CCR5(+/+) donor, and seven of eight isolates tested also infected CCR5(-/-) PBMCs. Analysis of coreceptor utilization using GHOST and U87 cell lines revealed that all of the isolates tested used CCR5 and the orphan receptors STRL33 and GPR15. Coreceptors such as CCR2b, CCR3, CCR8, and CX3CR1 were also utilized by some primary SIV isolates. More importantly, we found that CXCR4 was used as a coreceptor by the SIVstm, the SIVagm, and four of the SIVsm isolates in GHOST and U87 cells. These data suggest that primary SIV isolates from diverse primate species can utilize CXCR4 for viral entry, similar to what has been described for human immunodeficiency viruses.
Insights
Primary simian immunodeficiency viruses (SIV) can infect human cells using various coreceptors. Notably, some SIV strains utilize CXCR4, a pathway also used by human immunodeficiency viruses (HIV).
Area of Science:
- Virology
- Immunology
- Primate research
Background:
- Simian immunodeficiency virus (SIV) is a lentivirus that infects non-human primates.
- SIV is the precursor to human immunodeficiency virus (HIV).
- Understanding SIV coreceptor usage is crucial for studying HIV pathogenesis.
Purpose of the Study:
- To investigate the coreceptor usage of primary SIV isolates from diverse primate species.
- To determine if SIV can infect human cells and identify the specific coreceptors involved.
Main Methods:
- Primary SIV isolates from sooty mangabey, stumptail, mandrill, and African green primates were used.
- Infection of human peripheral blood mononuclear cells (PBMCs) from CCR5(+/+) and CCR5(-/-) donors was assessed.
- Coreceptor utilization was analyzed using GHOST and U87 cell lines, testing for CCR5, STRL33, GPR15, CCR2b, CCR3, CCR8, CX3CR1, and CXCR4.
Main Results:
- All tested SIV isolates infected human PBMCs.
- Seven of eight isolates infected CCR5(-/-) PBMCs, indicating CCR5-independent entry pathways.
- All isolates utilized CCR5, STRL33, and GPR15.
- Some isolates used CCR2b, CCR3, CCR8, and CX3CR1.
- Crucially, SIVstm, SIVagm, and four SIVsm isolates used CXCR4 for viral entry.
Conclusions:
- Primary SIV isolates exhibit broad coreceptor usage, including CCR5, STRL33, GPR15, and other chemokine receptors.
- The use of CXCR4 by diverse SIV isolates mirrors findings for human immunodeficiency viruses.
- These findings highlight potential shared mechanisms of viral entry between SIV and HIV, offering insights into cross-species transmission and viral adaptation.
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