Control of HIV infection by IFN-α: implications for latency and a cure

Bourke, Nollaig M.; Napoletano, Silvia; Bannan, Ciarán; Ahmed, Sibtain; Bergin, Colm; Stevenson, Nigel J.

doi:10.1007/s00018-017-2652-4

Cited by 18 publications

(15 citation statements)

References 96 publications

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“…HIV is rapidly detected by innate immune receptors (recently reviewed in Bourke et al 50 ), the PRRs; cGAS and IFI16, which detect viral cDNA. cGAS has been shown to be responsible for sensing of nascent HIV-1 cDNA in infected monocyte-derived dendritic cells and monocytes 51,52 where IFN production is then induced through the STING pathway and IRF3.…”

Section: Hiv Detection and Ifn Productionmentioning

confidence: 99%

Type I IFNs in the female reproductive tract: The first line of defense in an ever-changing battleground

Cumming

Bourke

2018

Journal of Leukocyte Biology

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The primary function of the female reproductive tract (FRT) is to enable successful reproduction, yet the biologic mechanisms required to accomplish this, which include fluctuating sex hormones and tolerance of semen and a semi-allogeneic fetus, can leave this unique mucosal environment susceptible to pathogenic challenge. Consequently, the FRT has evolved specialized innate and adaptive immune responses tailored to protecting itself from infection without compromising reproductive success. A family of innate immune cytokines that has emerged as important regulators of these immune responses is the type I IFNs. Type I IFNs are typically rapidly produced in response to pathogenic stimulation and are capable of sculpting pleotropic biologic effects, including immunomodulation, antiproliferative effects, and inducing antiviral and bactericidal molecules. Here, we review what is currently known about type I IFN-mediated immunity in the FRT in human, primate, and murine models and explore their importance with respect to three highly relevant FRT infections: HIV, Zika, and Chlamydia. K E Y W O R D SChlamydia, female reproductive tract, HIV, hormonal regulation, mucosal immunity, Type I IFNs, Zika THE FRT: A DYNAMIC IMMUNE ENVIRONMENTThe female reproductive tract (FRT) is a site of unique mucosal immune regulation; it must be capable of detecting and inducing immune responses against pathogenic infections yet maintain tolerance to commensal bacteria, semen, and the semi-allogeneic fetus. The FRT can be broadly divided into two main anatomic sites: the lower reproductive tract, which includes the vagina and ectocervix, and the upper reproductive tract, which includes the uterus, fallopian tubes, and ovaries. The structure of the lining of the FRT varies considerably between these sites and reflects their respective functional characteristics. The lining of the lower FRT comprises multilayered squamous epithelium, which represents a large barrier defense and supports high levels of commensal microbes. In contrast, the upper FRT comprises a single layer of columnar epithelium, which is remodeled in response to sex hormones to enable support of successful implantation and pregnancy. 1 Between these two sites of the FRT is the transformation zone, where the squamous epithelium of the ectocervix meets the columnar epithelium of the endocervix. FRT immunity is predominately mediated by both epithelial cells and the immune cells that underlie the epithelium in both the upper and lower reproductive tract. REGULATION OF FRT IMMUNITY: SEX HORMONESAn important aspect of immunoregulation within the FRT is that the FRT immune cells are continuously modulated in response to fluctuating levels of the sex hormones estrogen (E2) and progesterone (P4) during the menstrual cycle. The first line of defense against pathogen infection is usually the epithelial cells that line the upper and lower FRT. Epithelial cells that line the vagina and uterus are important regulators of immunity in the mucosa, acting through specialized antigen present...

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Section: Hiv Detection and Ifn Productionmentioning

confidence: 99%

Type I IFNs in the female reproductive tract: The first line of defense in an ever-changing battleground

Cumming

Bourke

2018

Journal of Leukocyte Biology

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“…C'est chez le macaque rhésus que cette activité antivirale de TRIM5α a été découverte en 2004 [4]. En effet, comme la plupart des singes, les macaques résistent à l'infection par le VIH-1 grâce à l'expression de cette protéine dans leurs cellules [5]. Les cellules humaines sont, quant à elles, incapables de bloquer le VIH-1, mais la protéine 1 Un motif présent dans plusieurs centaines de protéines humaines et impliqué dans les réactions d'ubiquitination.…”

Section: Les Facteurs De Restriction Rétroviraleunclassified

“…Cette régulation s'effectue initialement au niveau transcriptionnel puisque la plupart des facteurs de restriction ne sont pas ou peu transcrits constitutivement. Ils sont induits par les interférons de type 1, des cytokines sécrétées par les cellules infectées qui déclenchent une réponse antivirale dans les cellules avoisinantes afin de limiter la propagation virale [5]. Un autre niveau de régulation important est constitué par les modifications posttraductionnelles.…”

Section: Régulation Des Facteurs De Restrictionunclassified

SUMO régule la capacité de TRIM5α à inhiber le VIH-1

et al. 2019

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“…Upon viral infection, activation of the innate immune response mobilizes an antiviral state. Central to this process is the production of type 1 interferons (IFNs); these cytokines induce the expression of a cascade of IFN-stimulated genes (ISGs), many of which have direct antiviral properties (Doyle et al, 2015;Bourke et al, 2018). As with many viruses, HIV type-1 (HIV-1) replication is suppressed by the IFN response (reviewed by Doyle et al, 2015).…”

Section: Introductionmentioning

confidence: 99%