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Cloning and Characterization of Functional Subtype A HIV-1 Envelope Variants Transmitted Through Breastfeeding

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Previous studies of HIV-1 variants transmitted from mother-to-infant have focused primarily on computational analyses of partial envelope gene sequences, rather than analyses of functional envelope variants. There are very few examples of well-characterized functional envelope clones from mother-infant pairs, especially from envelope variants representing the most prevalent subtypes worldwide. To address this, we amplified the envelope variants present in 4 motherinfant transmission pairs, all of whom were infected with subtype A and three of whom presumably transmitted HIV-1 during the breastfeeding period. Functional envelope clones were constructed, either encoding full-length envelope sequences from the mother and baby or by making chimeric envelope clones in a common backbone sequence. The infant envelope sequences were genetically homogeneous compared to the maternal viruses, and pseudoviruses bearing these envelopes all used CCR5 as a coreceptor. The infant viruses were generally resistant to neutralization by maternal antibodies present near the time of transmission. There were no notable differences in sensitivity of the mother and infant envelope variants to neutralization by heterologous plasma or monoclonal antibodies 2G12 and b12, or to inhibition by sCD4, PSC-RANTES or TAK779. This collection of viral envelopes, which can be used for making pseudotyped viruses, may be useful for examining the efficacy of interventions to block mother-infant transmission, including sera from vaccine candidates, purified antibodies under consideration for passive immunization and viral entry inhibitors.

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Keywords: HIV-1; breastfeeding transmission; monoclonal antibodies; mother-infant transmission; neutralization

Document Type: Research Article

Affiliations: Division of Human Biology,Fred Hutchinson Cancer Center, 1100 Fairview Ave N., C3-168, Seattle,WA 98109-1024, USA.

Publication date: March 1, 2007

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  • Current HIV Research aims to cover all the latest and outstanding developments of HIV research. We invite comprehensive review articles and novel, pioneering work in the basic and clinical fields on all areas of HIV research, including virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Each issue of the journal contains a series of timely in-depth reviews and original research written by leaders in the field covering a range of current topics on HIV research. Periodically, the journal will invite guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
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