Related Experiment Videos
Restriction of HIV-1 (subtype B) replication at the entry step in rhesus macaque cells
1Department of Medical Pathology, University of California, Davis 95616, USA.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) is restricted for replication in rhesus macaque cells and does not establish infection in this species. The block to productive infection of macaque peripheral blood mononuclear cells (PBMC) in culture was investigated. A chimeric virus SHIV containing HIV-1 tat, rev, and env and all other genes from a simian immunodeficiency virus clone pathogenic in macaques (i.e., SIVmec239) replicated efficiently in macaque PBMC. Thus, the attachment step, involving interaction of the HIV-1 env glycoprotein with the cell surface CD4 receptor, is not blocked. Analysis of uptake of HIV-1 particles in these cells revealed a small reduction in virion entry; however, viral DNA synthesis, measured by PCR amplification, was greatly reduced. Taken together, these results indicate that the block to HIV-1 (subtype B) replication in rhesus macaque cells involves release of the virion core into the cytoplasm and/or a step immediately prior to initiation of reverse transcription. Further studies are required to characterize this block through identification of species-specific cellular proteins that interact with HIV-1 proteins in the early phase of viral replication.
Insights
Human immunodeficiency virus type 1 (HIV-1) cannot replicate in rhesus macaque cells. Research indicates the replication block occurs after viral entry but before reverse transcription, suggesting a post-entry restriction mechanism.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Human immunodeficiency virus type 1 (HIV-1) is a significant human pathogen.
- HIV-1 does not productively infect rhesus macaque cells, limiting in vivo research models.
- Understanding this species-specific restriction is crucial for developing effective antiviral strategies and animal models.
Purpose of the Study:
- To investigate the specific cellular barrier restricting HIV-1 replication in rhesus macaque peripheral blood mononuclear cells (PBMC).
- To identify the stage of the HIV-1 replication cycle that is blocked in macaque cells.
Main Methods:
- Construction and testing of a chimeric virus (SHIV) combining HIV-1 and SIV genes.
- Analysis of HIV-1 virion attachment, entry, and early replication steps in macaque PBMC.
- Quantification of viral DNA synthesis using PCR.
Main Results:
- The chimeric SHIV virus replicated efficiently in macaque PBMC, indicating attachment and CD4 interaction are not blocked.
- HIV-1 particle uptake showed only a minor reduction, but viral DNA synthesis was significantly impaired.
- The primary restriction point for HIV-1 in rhesus macaque cells occurs post-entry and pre-reverse transcription.
Conclusions:
- The block to HIV-1 replication in rhesus macaques is not at the attachment or entry stage.
- The restriction likely involves events related to virion core release or the initiation of reverse transcription.
- Further research is needed to identify specific host-cell factors responsible for this early-phase restriction.