Intriguing examples such as GPR35 for inflammatory bowel disease and CXCR4 for viral infection are used as illustrations of how a systematic approach can aid in the prioritization of interesting drug discovery hypotheses.
To investigate the effects of US27 on CXCR4 during virus infection, fibroblasts were infected with bacterial artificial chromosome-derived clinical strain HCMV TB40/E-<i>mCherry</i> (wild type [WT]), mutants lacking US27 (TB40/E-<i>mCherry</i>-US27Δ [US27Δ]) or all four GPCRs (TB40 E-<i>mCherry</i>-allΔ), or mutants expressing only US27 but not US28, UL33, or UL78 (TB40/E-<i>mCherry</i>-US27<i>wt</i> [US27<i>wt</i>]).
In conclusion, the chemokine receptors CCR5 and CXCR4 might influence virus replication during IBDV infection and further study would focus on the interaction between chemokine receptors and their ligands.
Among the chemokine receptors, CXCR4 stands out for its pleiotropic roles as well as for its involvement in several pathological conditions, including immune diseases, viral infections and cancer.
MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription and integration and productive viral infection.
To overcome this limitation, interleukin (IL)-4-transgenic hu-PBL-SCID mice were derived that spontaneously synthesized human IL-4, which has been shown to enhance CXCR4 expression and promote X4 virus infection in vitro.
CXCR4 and CCR5 strains of HIV were inhibited though an early stage in viral infection upstream of fusion, and a lack of inhibition of vesicular stomatitis virus G protein pseudotyped HIV-1 suggested the anti-HIV activity was relatively selective.
Stable simultaneous knock down of the HIV-1 coreceptors CCR5 and CXCR4 is a promising strategy to protect cells from both R5 macrophage tropic and X4 T cell tropic as well as dual tropic viral infections.
Interestingly, siRNAs targeting CXCR4 selectively inhibited CXCR4-tropic cell-free virus infection of human cells but at only modest levels as compared to cell:cell fusion. siRNA may be a potential molecular therapeutic approach to alter a cellular cofactor critical for infection of human cells by relevant strains of HIV-1.
Significant effect on virus infection in MAGI/CCR5 cells was neither observed for the X4 virus by capsianosides II, XI, and A, nor for an R5 virus by capsianoside G. Apparent enhancement of X4 HIV-1 infection by capsianoside G was observed and exclusively related to the usage of the CXCR4 coreceptor.