Overall, this strategy provided a concise genetic approach that revealed specific amino acid positions and side chain motifs in Vpr that were coselected with CXCR4 or
CCR5 coreceptor utilization during replication in HIV-1-infected patients.
In conclusion, our study documented for the first time a strong predictive association, independent from other available markers, that a high FPR, predicting a
CCR5 coreceptor usage, is protective in children and is related to a better immunological (CD4 level) and clinical outcome.
HIV-1 escape to
CCR5 coreceptor antagonism through selection of CXCR4-using variants in vitro.
Also, after work on polyanions began, research showed that viruses using the
CCR5 coreceptor are preferentially transmitted, and polyanions had even lower potency against those R5 viruses.
A
CCR5 coreceptor antagonist approved for use in combination with other anti-retroviral drugs for treating adults infected with only CCR5-tropic HIV-1 and who have evidence of viral replication and HIV-1 strains resistant to multiple anti-retroviral agents.
A
CCR5 coreceptor antagonist approved for use in combination with other antiretroviral drugs for treating adults infected with only CCR5-tropic HIV-1 and who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the
CCR5 coreceptor used by HIV to enter CD4-positive T cells.
Primary infection with HIV-1 is associated to macrophagetropic virus strains which infect mostly monocytes and macrophages bearing both the CD4 receptor and
CCR5 coreceptor. Although the
CCR5 coreceptor is required for chemokine signaling, individuals lacking the CCR5 alleles appear to have normal immune responses (56,57).
This drug blocks viral interaction with the
CCR5 coreceptor on the cell.
Factors such as the local inflammatory response caused by bacterial vaginosis, urethritis, and sexually transmitted diseases (STDs) have been associated with upregulation of
CCR5 coreceptor expression and increased activation of T lymphocytes in the mucosa of women, thus leading to increased susceptibility.
R5 exclusively uses
CCR5 coreceptors while X4 takes advantage of CXCR4 coreceptors and R5/X4 strains can use both [3].