Properties of the Surface Envelope Glycoprotein Associated with Virulence of Simian-Human Immunodeficiency Virus SHIVSF33A Molecular Clones
AUTOR(ES)
Chakrabarti, Lisa A.
FONTE
American Society for Microbiology
RESUMO
In vivo adaptation of simian-human immunodeficiency virus (SHIV) clone SHIVSF33 resulted in the emergence of pathogenic isolate SHIVSF33A, which caused a rapid and severe CD4+ T-cell depletion when inoculated into rhesus macaques. Two molecular clones generated by inserting the env V1-to-V5 region amplified from SHIVSF33A-infected animals into the parental SHIVSF33 genome retained a pathogenic phenotype. The gp120 envelope glycoproteins of pathogenic clones SHIVSF33A2 and SHIVSF33A5 conferred a threefold increase in viral entry and fusogenicity compared to the parental glycoprotein. Changes in gp120 were also responsible for a higher replication capacity and cytopathicity in primary CD4+ T-cell cultures. Last, gp120 carried the determinants of SHIVSF33A neutralization resistance. Thus, changes in SHIVSF33A gp120 produced a set of properties that could account for the pathogenic phenotype observed in vivo. Measurement of antibody binding to SHIVSF33A viral particles revealed an increased exposure of the CD4-induced epitope recognized by the 17b monoclonal antibody in a region that was shown to contribute to coreceptor binding. Exposure of this epitope occurred in the absence of CD4 binding, suggesting that the envelope glycoprotein of pathogenic SHIVSF33A clones folded in a conformation that was primed for interaction with CXCR4 or for the subsequent step of fusion.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=135897Documentos Relacionados
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