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Structural Characterization of Genetic Elements in HIV-1 V3 Loop Regulation

Research on the interaction between HIV-1gp120, CD4 receptor, and CCR5 or CXCR4 in determining coreceptor usage. Discoveries on V3 loop regions and mutations affecting coreceptor selection made from Huang et al.'s analysis. This study analyzed 323 blood samples to identify specific V3 sequence positions linked to CCR5 or CXCR4 usage. 29 mutations were examined, with 6 identifying CCR5 selection and 23 for CXCR4. This research highlights the crucial role of V3 base interaction with CCR5 in HIV infection.

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Structural Characterization of Genetic Elements in HIV-1 V3 Loop Regulation

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  1. PubMed Research Article • “Identification and structural characterization of novel genetic elements in the HIV-1 V3 loop regulation coreceptor usage” by Svicher et al. • Studied the interaction between HIV-1gp120 and CCR5 N terminus

  2. HIV-1 entry involves gp120, CD4 recepor and CCR5 or CXCR4 • V3 loop is determining factor in coreceptor usage • Composed of 3 regions • Base • Stem • Hairpin crown • V3 positions 11, 24 and 25 bind with different coreceptors but mechanism that differentiates is not know

  3. V3 base interaction with CCR5 critical for infection • Increased affinity of V3 for CCR5 • Study population: 323 blood samples from 323 HIV-1 patients • V3 mutation was tested for along with wild-type residues to see different coreceptor usage • Structural analysis taken from Huang et al. CCR5 model with HIV-1 gp120

  4. V3 sequence determines coreceptor usage • 19 V3 sequence positions that correlated to CCR5 of CXCR4 usage • Of 29 mutations, 6 are at the V3 positions of 11, 24 and 25 select for CCR5 • 23 other mutations at 15 V3 positions select for CXCR4 • Mutations for CCR5 not seen in viruses that select for CXCR4 and vice versa • Less that 1% of mutation in each case

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