Disease progression during human immunodeficiency virus type 1 (HIV-1) infection has been associated with a switch of viral coreceptor usage from CCR5 to CXCR4.
The finding is relevant as regards the fact that SDF1-3'A polymorphism induces an increase of SDF1 chemokine production, in which it competes with HIV-1 in binding to CXCR4 receptor, and in turn inhibits HIV-1 infection.
Down regulation of CCR5 and CXCR4 after HIV-1 infection could be the result of indirect events linked to HIV-1 infection, such as the induction of alpha- or beta-chemokines competing with the virions for receptor binding.
The chemokine receptorCXCR4/stromal cell-derived factor-1 (SDF-1: CXCL12) signaling axis represents a crucial drug target due to its relevance to several diseases such as HIV-1 infection, cancer, leukemia, and rheumatoid arthritis.
Human immunodeficiency virus (HIV)-resistant CD4+ UT-7 megakaryocytic human cell line becomes highly HIV-1 and HIV-2 susceptible upon CXCR4 transfection: induction of cell differentiation by HIV-1 infection.
Coreceptor switching from CCR5 to CXCR4 is common during chronic HIV-1 infection, but is even more common in individuals who have failed antiretroviral therapy (ART).
Carriers of the deltaccr5 allele, which contains a deletion of 32 bases in relation to the normal allele of the beta-chemokine receptor gene (CCR5), have increased resistance to HIV-1 infection.
Using HIV-1 challenge assays, we demonstrated that CXCR4-tropic or CCR5-tropic HIV-1 infections were significantly reduced in <i>CXCR4</i>- and <i>CCR5</i>-modified cells, and the modified cells exhibited a selective advantage over unmodified cells during HIV-1 infection.
CXCR4 is a frequent alternative coreceptor (CoR) in subtype B and D HIV-1 infection, but the importance of many other alternative CoRs remains elusive.
High plasma SDF-1 levels and low CXCR4 expression on T lymphocytes was associated with long-term nonprogression, whereas in advancing disease expression of CXCR4 increased, accompanied by a decrease in plasma SDF-1 during the more advanced stages of HIV-1 infection.
Understanding the role of CXCR4 and other chemokine receptors in HIV-1 neuropathogenesis will help to advance the development of new therapeutic strategies for the prevention and treatment of neurologic disorders associated with HIV-1 infection.
Our study demonstrates that individuals may be infected by minority X4 viruses from a population that predominately uses CCR5 for entry, and that viruses may bypass traditional HIV-1 coreceptors (CCR5 and CXCR4) completely by engaging alternative coreceptors to establish and propagate HIV-1 infection.
This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.
This study analyzed the SDF1-3'A SNP and performed mutation screening for polymorphic markers in the CXCR4 gene to determine the presence or absence of significant associations with susceptibility to HIV-1 infection.