Enhanced Macrophage Tropism of HIV in Brain and Lymphoid Tissues is Associated with Sensitivity to the Broadly Neutralizing CD4 Binding Site Antibody b12

DSpace/Manakin Repository

Enhanced Macrophage Tropism of HIV in Brain and Lymphoid Tissues is Associated with Sensitivity to the Broadly Neutralizing CD4 Binding Site Antibody b12

Citable link to this page

. . . . . .

Title: Enhanced Macrophage Tropism of HIV in Brain and Lymphoid Tissues is Associated with Sensitivity to the Broadly Neutralizing CD4 Binding Site Antibody b12
Author: Dunfee, Rebecca L; Thomas, Elaine R; Gabuzda, Dana Helga

Note: Order does not necessarily reflect citation order of authors.

Citation: Dunfee, Rebecca L., Elaine R. Thomas, and Dana Helga Gabuzda. 2009. Enhanced macrophage tropism of HIV in brain and lymphoid tissues is associated with sensitivity to the broadly neutralizing CD4 binding site antibody b12. Retrovirology 6: 69.
Full Text & Related Files:
Abstract: Macrophages in the central nervous system (CNS) and other tissues are an important cellular reservoir for human immunodeficiency virus type 1 (HIV) infection, particularly in the later stages of disease. Macrophage-tropic HIV strains have an enhanced capacity to enter cells expressing low levels of CD4 through mechanisms that are not well understood. Here, we use a panel of primary HIV envelopes from brain and lymphoid tissues to examine the relationship between neutralization sensitivity to reagents targeting the CD4 binding site and virus entry into macrophages. Neutralization assays using pseudotyped viruses showed an association between the capacity of HIV to enter macrophages and increased sensitivity to the broadly neutralizing monoclonal antibody (mAb) b12, which recognizes a conserved epitope overlapping the CD4 binding site, but not sensitivity to soluble CD4 (sCD4) or b6, a non-neutralizing CD4 binding site mAb. Furthermore, loss of an N-linked glycosylation site at position 386 in the V4 region of Env enhanced macrophage tropism together with b12 sensitivity, but not neutralization by sCD4, b6, or a broadly neutralizing AIDS patient serum. These findings suggest that exposure of the b12 epitope, rather than exposure of the CD4 binding site per se, enhances HIV macrophage tropism, possibly by exposing a region on the outer domain of gp120 that is initially recognized by CD4. These findings suggest overlap between specific gp120 determinants in or near the b12 epitope and those conferring macrophage tropism.
Published Version: doi:10.1186/1742-4690-6-69
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717910/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4728496

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters