Journal
VIROLOGY
Volume 360, Issue 2, Pages 294-304Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2006.10.027
Keywords
2G12; resistance; glycosylation; gpl20; mannose-specific lectins
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The 2G12 mAb inhibits the infection of HIV-1 laboratory-adapted viruses at 50% inhibitory concentrations (IC50) ranging from 0.02 to 0.2 mu g/ ml when evaluated in different cell-types. However, isolates from various HIV-1 subtypes (such as clade C, D, A/E, F and group 0) were not inhibited by 2G12 mAb (IC50 >20 mu g/ml). 2G12 mAb pressure in HIV-1 IIIB- and NL4.3-infected T cell cultures selected for resistant viruses containing only few (1 to 3 N-glycosylation) deletions in gp120. The 2G12-resistant viruses keep their full sensitivity to various mannose-specific lectins and other known HIV entry inhibitors. Moreover, we observed that the NL4.3-2G12-resistant virus, with the N295K mutation in gp120, became significantly more sensitive to several mannose-specific lectins. This is, to our knowledge, the first report showing that a resistant virus generated in vitro against a neutralizing mAb and containing a mutation in gp120, has increased sensitivity to another class of HIV entry inhibitors. (c) 2006 Elsevier Inc. All rights reserved.
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