Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection<i>In Vivo</i>

Lavender, Kerry J.; Gibbert, Kathrin; Peterson, Karin E.; Dis, Erik Van; Francois, Sandra; Woods, Tyson A.; Messer, Ronald J.; Gawanbacht, Ali; Müller, Janis A.; Münch, Jan; Phillips, Katie; Race, Brent; Harper, Michael S.; Guo, Kejun; Lee, Eric J.; Trilling, Mirko; Hengel, Hartmut; Piehler, Jacob; Verheyen, Jens; Wilson, Cara C.; Santiago, Mario L.; Hasenkrug, Kim J.; Dittmer, Ulf

doi:10.1128/jvi.00451-16

Cited by 112 publications

(204 citation statements)

References 85 publications

(120 reference statements)

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“…These results indicate that additional factors, possibly including IFNα2 and/or other IFN subtypes, shape the transmitted founder phenotype. Because there are a total of 13 IFNα subtypes as well as other type 1 IFNs such as IFNω, some of which inhibit HIV-1 even more potently in vitro and in animal models (79)(80)(81), it will be critical to evaluate to what extent they contribute alone, or in combination, to the HIV-1 transmission bottleneck. Fig.…”

Section: Discussionmentioning

confidence: 99%

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness

Iyer

Bibollet-Ruche

Sherrill-Mix

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

131

180

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Sexual transmission of HIV-1 is an inefficient process, with only one or few variants of the donor quasispecies establishing the new infection. A critical, and as yet unresolved, question is whether the mucosal bottleneck selects for viruses with increased transmission fitness. Here, we characterized 300 limiting dilution-derived virus isolates from the plasma, and in some instances genital secretions, of eight HIV-1 donor and recipient pairs. Although there were no differences in the amount of virion-associated envelope glycoprotein, recipient isolates were on average threefold more infectious (P = 0.0001), replicated to 1.4-fold higher titers (P = 0.004), were released from infected cells 4.2-fold more efficiently (P < 0.00001), and were significantly more resistant to type I IFNs than the corresponding donor isolates. Remarkably, transmitted viruses exhibited 7.8-fold higher IFNα2 (P < 0.00001) and 39-fold higher IFNβ (P < 0.00001) half-maximal inhibitory concentrations (IC 50 ) than did donor isolates, and their odds of replicating in CD4 + T cells at the highest IFNα2 and IFNβ doses were 35-fold (P < 0.00001) and 250-fold (P < 0.00001) greater, respectively. Interestingly, pretreatment of CD4 + T cells with IFNβ, but not IFNα2, selected donor plasma isolates that exhibited a transmitted virus-like phenotype, and such viruses were also detected in the donor genital tract. These data indicate that transmitted viruses are phenotypically distinct, and that increased IFN resistance represents their most distinguishing property. Thus, the mucosal bottleneck selects for viruses that are able to replicate and spread efficiently in the face of a potent innate immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness

Iyer

Bibollet-Ruche

Sherrill-Mix

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

131

180

View full text Add to dashboard Cite

show abstract

“…It has been shown that IFN-Is can suppress HIV-1 replication in vitro (3). IFN-Is have also been shown to inhibit initial simian immunodeficiency virus (SIV) infection in rhesus macaques (7) and HIV-1 infection in humanized mice (8,9) in vivo. Furthermore, reports also indicated that transmitted/founder viruses isolated from patients are less sensitive to suppression by IFN-α in cultured cells than their corresponding viruses present during chronic infection, suggesting that resistance to IFN-Imediated inhibition may provide a selective advantage during transmission and initial infection (10,11).…”

Section: Introductionmentioning

confidence: 99%

Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection

Liu¹,

Yu²,

Li³

et al. 2017

JCI Insight

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“…It has been reported that IFN-I can suppress HIV-1 replication in vitro (5), and the major anti-HIV-1 restriction factors are encoded by ISGs (5). In addition, IFN-I has been shown to inhibit early HIV-1 infection in humanized mice (hu-mice) (9) and SIV infection in rhesus macaques in vivo (10). These observations suggest that a robust IFN-I response helps to control or limit initial HIV-1 and SIV infection.…”

Section: Introductionmentioning

confidence: 99%

Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs

Liu¹,

Ma²,

Li³

et al. 2016

Journal of Clinical Investigation

156

223

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Interferon Alpha Subtype-Specific Suppression of HIV-1 InfectionIn Vivo

Abstract: Although all 12 subtypes of human interferon alpha (IFN-␣

Cited by 112 publications

References 85 publications

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness

Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection

Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs

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