2013
DOI: 10.1186/1742-4690-10-146
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Relative resistance of HIV-1 founder viruses to control by interferon-alpha

Abstract: BackgroundFollowing mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in es… Show more

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Cited by 186 publications
(240 citation statements)
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References 102 publications
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“…We previously reported that TF viruses are more resistant to IFNα2 than viruses from chronically infected individuals (26,52). However, two subsequent studies of linked transmission pairs failed to confirm this phenotype, with one study finding no differences in IFNα2 resistance between transmitted and nontransmitted viruses (27), and the other reporting transmitted viruses being more IFNα2 sensitive (28).…”
Section: Fold Increase In Env Contentmentioning
confidence: 82%
“…We previously reported that TF viruses are more resistant to IFNα2 than viruses from chronically infected individuals (26,52). However, two subsequent studies of linked transmission pairs failed to confirm this phenotype, with one study finding no differences in IFNα2 resistance between transmitted and nontransmitted viruses (27), and the other reporting transmitted viruses being more IFNα2 sensitive (28).…”
Section: Fold Increase In Env Contentmentioning
confidence: 82%
“…IFN-␣14 was 10.8-fold more potent (in picograms per milliliter), 13.6-fold more potent (in units per milliliter), and 11.0-fold more potent (nanomolar) than IFN-␣2. IFN-␣14 also inhibited HIV-1 with greater potency than IFN-␣2 at maximal IFN-␣ concentrations, as there was more residual HIV-1 replication (V res ) (45) in HIV-1-infected LPMCs treated with IFN-␣2 (V res ϭ 40%) versus IFN-␣14 (V res ϭ 30%). Based on these results, IFN-␣14 was selected for in vivo studies in HIV-1-infected humanized mice using the clinically approved IFN-␣2 subtype as the comparison control.…”
Section: Antiviral Activities Of Ifn-␣ Subtypes On Hiv-1 Replication mentioning
confidence: 99%
“…pNL43-ADA(Env)-GFP.IRES.Nef proviral vectors (deleted for vpu, nef, and nef and vpu or expressing the D368R Env variant) and the VSVG-encoding plasmid (pSVCMV-IN-VSV-G) were previously described (12,51). T/F and corresponding 6-mo consensus IMCs of patients CH58 and CH77 were inferred, constructed, and biologically characterized as described (36)(37)(38)(39).…”
Section: Methodsmentioning
confidence: 99%
“…To ensure that sensitization of HIV-1-infected cells by CD4 mimetics was also observed when using full-length clinically relevant primary HIV-1 isolates, we infected primary CD4 T cells with extensively characterized infectious molecular clones (IMCs) constructed from two transmitted/founder (T/F) and their corresponding 6-mo consensus sequences (36)(37)(38)(39). Primary viruses are known to exhibit low Env reactivity and, as such, have little or no intrinsic exposure of CD4i epitopes (40).…”
Section: Cd4 Mimetics Enhance Recognition and Killing Of Cells Infectmentioning
confidence: 99%