Generation of Transmitted/Founder HIV-1 Infectious Molecular Clones and Characterization of their Replication Capacity in CD4 T-Lymphocytes and Monocyte-derived Macrophages

摘要: ABSTRACT Genome sequences of transmitted/founder (T/F) HIV-1 have been inferred by analyzing single genome amplicons acute infection plasma viral RNA in the context a mathematical model random virus evolution; however, few these T/F molecularly cloned and biologically characterized. Here, we describe derivation biological analysis ten infectious molecular clones, each representing responsible for productive clade B clinical infection. Each viruses primarily utilized CCR5 coreceptor entry replicated efficiently primary human CD4 + T lymphocytes. This result supports conclusion that amplification-derived from allow inference genomes are consistently replication competent. Studies with monocyte-derived macrophages (MDM) demonstrated various levels among viruses. Although all MDM, overall efficiency was significantly lower compared to prototypic “highly macrophage-tropic” strains. phenotype transferable expressing env genes an isogenic proviral DNA backbone, indicating macrophage tropism mapped Env. Furthermore, higher concentrations soluble were required inhibit macrophage-tropic Our findings suggest acquisition subtype occurs mucosal exposure is not highly tropic generation initial characterization 10 clones provides new opportunities probe virus-host interactions involved transmission.