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• W2047404769 abstract "Similar to HIV, FIV uses a two-receptor mechanism to infect CD4(+) T cells, the primary target cells in the cat. The T cell activation marker, CD134, serves as a primary binding receptor similar to the role of CD4 for HIV and facilitates interaction with the entry receptor, CXCR4. Heparan sulfate proteoglycans (HSPG) can also act as binding receptors for certain tissue culture adapted FIV and HIV isolates. In the present study, we employed site-directed mutagenesis to investigate the importance of specific residues on the FIV envelope for CD134 and HSPG interactions. We show that certain mutations that disrupt CD134 interactions facilitate HSPG binding by FIV-PPR. In particular, an E407K mutation at the base of the V3 loop knocks out CD134 binding; enhances HSPG binding; and in combination with additional Env mutations E656K and V817I increases entry into CD134(-), CXCR4(+) target cells by greater than 80-fold over wild type FIV-PPR. The CD134-independent mutant, termed FIV-PPRcr, exhibits a broadened host cell range, but also becomes readily susceptible to CD134-dependent neutralizing monoclonal antibodies. The findings are consistent with the notion that FIV-PPRcr Env has an open conformation that readily associates with CXCR4 directly, similar to wild type FIV-PPR Env after CD134 binding. The findings highlight the utility of a two-receptor mechanism that allows FIV V3 residues critical for CXCR4 binding to remain cryptic until reaction occurs with the primary binding receptor, thus thwarting immune surveillance." @default.
• W2047404769 created "2016-06-24" @default.
• W2047404769 creator A5010105396 @default.
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• W2047404769 date "2012-07-01" @default.
• W2047404769 modified "2023-09-25" @default.
• W2047404769 title "Mapping of Receptor Binding Interactions with the FIV Surface Glycoprotein (SU); Implications Regarding Immune Surveillance and Cellular Targets of Infection" @default.
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• W2047404769 doi "https://doi.org/10.4137/rrt.s9429" @default.
• W2047404769 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3523734" @default.
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• W2047404769 hasPublicationYear "2012" @default.
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