Scientists have genetically engineered mice not to express the CXCR4 coreceptor
. These mice did not survive long enough to be born and the embryos showed serious abnormalities to their immune systems, hearts and central nervous systems.
Given that HIV-1 could use either CCR5 or CXCR4 coreceptors in its entry to the cell, we needed to assess if PSP had a direct impact on the expression of a chemokine CXCR4 ligand receptor, SDF-1[alpha].
The antiviral environment created by this signaling cascade would allow the immune system to repress HIV-1 replication by blocking viral entry through the CCR5 and CXCR4 coreceptors. The overall implications of these findings suggest that PSP induces an anti-HIV-1 response mediated by TLR4 activation and antiviral chemokine response.
R5 exclusively uses CCR5 coreceptors while X4 takes advantage of CXCR4 coreceptors
and R5/X4 strains can use both .
On the other hand, viruses able to use CXCR4 coreceptors
(X4-tropic) tend to emerge later in the course of HIV infection, in comparison with R5 strains, and are recognized in nearly half of patients with advanced disease stages.
The limitation of our study include the absence of detection of HIV tropism to CCR5 and CXCR4 coreceptors
and correlations of HIV tropism with immunological and clinical data of HIV-infected patients involved in the study.
* Virus has capacity to use both CCR5 and CXCR4 coreceptors
for attachment and entry into CD4 lymphocytes.
The CCR5 and CXCR4 coreceptors
are required for proper viral entrance to CD4-bearing monocytes and T lymphocytes, by macrophagetropic and lymphotropic vimses, respectively.