Mucosal Tissue Tropism and Dissemination of HIV-1 Subtype B Acute Envelope-Expressing Chimeric Virus

King, Deborah; Siddiqui, Asna A.; Buffa, Viviana; Fischetti, Lucia; Gao, Yong; Stieh, Daniel J.; McKay, Paul F.; Rogers, P. S. Z.; Ochsenbauer, Christina; Kappes, John C.; Arts, Eric J.; Shattock, Robin J.

doi:10.1128/jvi.02216-12

Cited by 23 publications

(39 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with these findings, most macrophage-tropic SIV clones are highly neutralization sensitive. Together with previous studies suggesting that most transmitted/founder viruses replicate poorly in macrophages (Isaacman-Beck et al, 2009; King et al, 2013; Li et al, 2010; Ochsenbauer et al, 2012; Salazar-Gonzalez et al, 2009), these findings led to the prevailing view that macrophage-tropic HIV/SIV variants are rare or absent during early-stage infection.…”

Section: Introductionmentioning

confidence: 67%

Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques

et al. 2014

View full text Add to dashboard Cite

Macrophages play an important role in HIV/SIV pathogenesis by serving as a reservoir for viral persistence in brain and other tissues. Infected macrophages have been detected in brain early after infection, but macrophage-tropic viruses are rarely isolated until late-stage infection. Little is known about early variants that establish persistent infection in brain. Here, we characterize a unique macrophage-tropic SIV envelope glycoprotein (Env) variant from two weeks post-infection in blood of an SIVmac251-infected macaque that is closely related to sequences in brain from animals with neurological disease. SIVmac251 clones expressing this Env are highly fusogenic, and replicate efficiently in T cells and macrophages. N173 and N481 were identified as novel determinants of macrophage tropism and neutralization sensitivity. These results imply that macrophage-tropic SIV capable of establishing viral reservoirs in brain can be present in blood during early infection. Furthermore, these SIVmac251 clones will be useful for studies on pathogenesis, eradication, and vaccines.

show abstract

Section: Introductionmentioning

confidence: 67%

Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques

et al. 2014

View full text Add to dashboard Cite

show abstract

“…35,61 Laboratory-adapted HIV-1 BaL , on the other hand, infects CD4 + T cells through CD4 + receptors and CCR5 coreceptors but does not utilize CXCR4. 64 It infects monocyte-derived macrophages as well as CD4 + T cells whereas HIV-1 CH077 infects primarily CD4 + T cells and macrophages only inefficiently. 35 How this relates to the kinetics of viral replication observed in these studies is unclear; however, there may be some evidence of more efficient infection in the HIV-1 CH077 -infected biopsies due to the higher levels of HIV-1 RNA at early time points after infection.…”

Section: Fig 4 (A)mentioning

confidence: 99%

The Molecular Characterization of Intestinal Explant HIV Infection Using Polymerase Chain Reaction-Based Techniques

Janocko

Althouse

Brand

et al. 2015

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

“…This may have particular relevance given the potential role of mucosal antigen-presenting cells in the uptake and subsequent presentation of HIV-1 to CD4 + target cells (18–21), facilitating dissemination through cis - and trans -infection pathways (22). Additionally, phagocytosis of opsonized virions may itself reduce the probability of successful infection of tissue resident CD4 + T cells, the primary targets of mucosal infection in humans and macaques, by reducing the half-life of infectious virus (23–25). …”

Section: Introductionmentioning

confidence: 99%

Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies

Cheeseman

Olejniczak

Rogers

et al. 2017

J Virol

Self Cite

View full text Add to dashboard Cite

Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-mediated neutralization is highly effective against cell-free virus, antibodies targeting different sites of envelope vulnerability may display differential activity against mucosal infection. Nonneutralizing antibodies (nnAbs) may also impact mucosal transmission events through Fc-gamma receptor (FcγR)-mediated inhibition. In this study, a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protection in the RV144 vaccine trial, were screened for the ability to block HIV-1 acquisition and replication across a range of cellular and mucosal tissue models. Neutralization potency, as determined by the TZM-bl infection assay, did not fully predict activity in mucosal tissue. CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking HIV-1 infection across all cellular and tissue models. Membrane-proximal external region (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of mucosal tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more variable. In contrast, nnAbs alone and in combinations, while active in a range of cellular assays, were poorly protective against HIV-1 infection of mucosal tissues. These data suggest that tissue resident effector cell numbers and low FcγR expression may limit the potential of nnAbs to prevent establishment of the initial foci of infection. The solid protection provided by specific bnAbs clearly demonstrates their superior potential over that of nonneutralizing antibodies for preventing HIV-1 infection at the mucosal portals of infection. IMPORTANCE Key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue have not been defined. While bnAbs are highly effective against cell-free virus, they are not induced by current vaccine candidates. However, nnAbs, readily induced by vaccines, can trigger antibody-dependent cellular effector functions, through engagement of their Fc-gamma receptors. Fc-mediated antiviral activity has been implicated as a secondary correlate of decreased HIV-1 risk in the RV144 vaccine efficacy trial, suggesting that protection might be mediated in the absence of classical neutralization. To aid vaccine design and selection of antibodies for use in passive protection strategies, we assessed a range of bnAbs and nnAbs for their potential to block ex vivo challenge of mucosal tissues. Our data clearly indicate the superior efficacy of neutralizing antibodies in preventing mucosal acquisition of infection. These results underscore the importance of maintaining the central focus of HIV-1 vaccine research on the induction of potently neutralizing antibodies.

show abstract

Mucosal Tissue Tropism and Dissemination of HIV-1 Subtype B Acute Envelope-Expressing Chimeric Virus

Cited by 23 publications

References 48 publications

Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques

Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques

The Molecular Characterization of Intestinal Explant HIV Infection Using Polymerase Chain Reaction-Based Techniques

Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies

Contact Info

Product

Resources

About