2012
DOI: 10.1371/journal.ppat.1002686
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Transmitted/Founder and Chronic Subtype C HIV-1 Use CD4 and CCR5 Receptors with Equal Efficiency and Are Not Inhibited by Blocking the Integrin α4β7

Abstract: Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and short… Show more

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Cited by 139 publications
(192 citation statements)
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“…30,35,65 Furthermore, V2 contains a putative a 4 b 7 integrin-binding motif of uncertain significance. 39 Although 1454 KARASAVVAS ET AL.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…30,35,65 Furthermore, V2 contains a putative a 4 b 7 integrin-binding motif of uncertain significance. 39 Although 1454 KARASAVVAS ET AL.…”
Section: Discussionmentioning
confidence: 99%
“…23,24,37,38 However, further studies are needed to confirm the role of a 4 b 7 in viral transmission with unliganded gp120 trimers. 39 Broadly neutralizing antibodies that interact with quaternary neutralizing epitopes (QNE) of trimeric native Env spikes have been shown to interact with conserved aa embedded within the variable (V) loops of gp120 including the V2 loop. [40][41][42][43][44][45][46][47] Furthermore, antibodies found in individuals that exhibit potent cross-clade neutralizing activity have been shown to target conserved regions of the V1, V2, and V3 loops, providing evidence that V2 contributes to the formation of QNE that can induce potent cross-clade neutralizing antibodies.…”
Section: Introductionmentioning
confidence: 99%
“…in activated CD4 + T cells but not macrophages (14,(22)(23)(24)(25). Moreover, analysis of a comprehensive panel of infectious molecular clones (IMCs) showed that TF viruses packaged more envelope glycoprotein (Env), exhibited greater infectivity, bound to monocyte-derived dendritic cells more efficiently, and replicated to higher titers in CD4 + T cells in the presence of the type 1 interferon IFNα2 than chronic control (CC) viruses (26).…”
mentioning
confidence: 99%
“…of protection-encompassing proviral infectious molecular clones (IMC) of transmitter/founder (T/F) HIV-1 [4][5][6] and several forms of reporter virus derivatives expressing genes such as enhanced green fluorescent protein (EGFP) 7 and Renilla luciferase (LucR), 4,8 which underpin new immune monitoring assays and augment the performance of existing assays for various vaccine discovery approaches. 3,4,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Among formerly described replication-competent HIV-1 reporter vectors were those designed with a bicistronic EGFP-IRES-nef cassette in place of nef, in which the EGFP gene is downstream of env, and nef is under translational control of an internal ribosome entry site (IRES) from encephalomyocarditis virus (EMCV).…”
mentioning
confidence: 99%