Related Experiment Videos
Early- and intermediate-stage variants of simian immunodeficiency virus replicate efficiently in cells lacking CCR5
Serene Forte1, Mary-Elizabeth Harmon, Mario J Pineda
1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Abstract:
Primate lentiviruses are thought to use the chemokine receptor CCR5 as the major coreceptor for entry into cells. Here we show that some variants of simian immunodeficiency virus (SIV) replicate efficiently in peripheral blood mononuclear cells (PBMCs) lacking a functional CCR5. There were differences in the replication patterns of sequential variants that evolved during SIVMne infection; the late-stage pathogenic variants were unable to replicate in PBMCs lacking CCR5, whereas the early- and intermediate-stage viruses replicated as well in PBMCs lacking CCR5 as they did in cells with wild-type CCR5. The coreceptor specificities of these sequential variants were compared using indicator cell lines expressing known SIV coreceptors. Among the known SIV coreceptors, there were none that were functional for the early and intermediate variants but not the late-stage variants, suggesting that the coreceptor used for replication in PBMCs may be a coreceptor that has not yet been described. Because some variants replicate with high efficiency in peripheral blood cells using this as yet uncharacterized cellular receptor, this coreceptor may be important for viral entry of some target cell populations in the host.
Insights
Some simian immunodeficiency virus (SIV) variants can infect cells without the typical CCR5 coreceptor. Early-stage SIV evolved to use an uncharacterized receptor, crucial for viral entry into host cells.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Primate lentiviruses, including simian immunodeficiency virus (SIV), primarily utilize the chemokine receptor CCR5 for cellular entry.
- Understanding viral coreceptor usage is critical for deciphering host-pathogen interactions and viral pathogenesis.
Purpose of the Study:
- To investigate the coreceptor usage of different simian immunodeficiency virus (SIV) variants during infection.
- To identify potential novel cellular receptors involved in SIV replication in peripheral blood mononuclear cells (PBMCs).
Main Methods:
- Comparative replication assays of sequential SIV variants in PBMCs with and without functional CCR5.
- Coreceptor specificity analysis using indicator cell lines expressing known SIV coreceptors.
Main Results:
- Certain SIV variants demonstrated efficient replication in PBMCs lacking functional CCR5.
- Early- and intermediate-stage SIV variants replicated effectively in CCR5-negative PBMCs, unlike late-stage pathogenic variants.
- No known SIV coreceptors fully explained the differential replication patterns observed.
Conclusions:
- SIV replication in PBMCs can occur independently of CCR5, suggesting the involvement of alternative coreceptors.
- An uncharacterized cellular receptor may mediate the entry of specific SIV variants into target cells.
- This novel coreceptor could play a significant role in SIV pathogenesis and viral spread within host populations.