Progress and Perspectives on HIV-1 microbicide development

Alexandre, Kabamba B.; Mufhandu, Hazel Tumelo; London, G; Chakauya, Ereck; Khati, Makobetsa

doi:10.1016/j.virol.2016.07.004

Cited by 25 publications

(22 citation statements)

References 190 publications

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“…As for these viruses, topical microbicides developed and formulated for vaginal use44 should be considered among the preventative strategies against ZIKV infection.…”

Section: Discussionmentioning

confidence: 99%

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

Pagani

Ghezzi

Ulisse

et al. 2017

Sci Rep

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“…As for these viruses, topical microbicides developed and formulated for vaginal use44 should be considered among the preventative strategies against ZIKV infection.…”

Section: Discussionmentioning

confidence: 99%

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

Pagani

Ghezzi

Ulisse

et al. 2017

Sci Rep

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“…The development of topical microbicides (TM) to protect against sexual mucosal transmission is a priority in HIV research. In the absence of a vaccine, the promise of anti-HIV TM is to allow receptive sexual partners, especially women in developing countries, greater control over their protection from HIV and other sexually transmitted diseases (93,94). A cervicovaginally applied gel has received the most attention thus far, and intravaginal rings and films dispensing antivirals over extended periods are also in development (95,96).…”

Section: Discussionmentioning

confidence: 99%

Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene

Chan

Trinité

Levy

2017

Antimicrob Agents Chemother

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HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations.KEYWORDS resting CD4 T cells, human immunodeficiency virus, pterostilbene, resveratrol, reverse transcription, stilbenoid, PrEP T he stilbenoids resveratrol (RES) and pterostilbene (PTE) function as plant phytoalexins, i.e., defensive compounds generated in response to parasitic attack. Resveratrol is found in grape skins, small berries, peanuts, and some nuts and has been extensively studied as an active ingredient of red wine, contributing to the health benefits associated with the French paradox and other potential life-extending properties, including anti-inflammatory, anticancer, and antidiabetes activities (1). Pterostilbene is a natural dimethylated analog of resveratrol also found in grape skins, berries, peanuts, and almonds (2). Pterostilbene has anti-inflammatory activity (3, 4), is more lipophilic than resveratrol, and has greater stability in vitro and in vivo (5-8).Resveratrol inhibits the replication of several viruses, including herpes simplex viruses (HSVs) 1 and 2, varicella-zoster virus, papillomaviruses, and influenza virus (9-12). Topical application of resveratrol has been found to inhibit HSV vaginal transmission in mice, suggesting that it might be useful as a topical microbicide (13). Alone, resveratrol does not inhibit wild-type (WT) human immunodeficiency virus type 1 (HIV-1) replication in activated T cells or in transformed T cell lines (14, 15), but it does potentiate inhibition of reverse transcription by nucleoside analog reverse transcriptase (RT) inhibitors (NRTIs), including tenofovir (TFV), didanosine, zidovudine (AZT), and emtricitabine (FTC) (14,16). Resveratrol alone does, however, inhibit reverse transcription in NRTI-resistant RT muta...

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“…As for these viruses, topical microbicides developed and formulated for vaginal use 44 should be considered among the preventative strategies against ZIKV infection. Plaque Forming Assay (PFA).…”

Section: Discussionmentioning

confidence: 99%

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

Pagani

Ghezzi

Ulisse

et al. 2016

Preprint

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Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred . A global health emergency was triggered at the end of 2015 by the observation of an increased incidence of microcephaly that was associated with the temporal and geographic distribution of ZIKV infection in the North East Brazil 4 . Increasing evidence now clearly supports a cause-effect relationship between congenital ZIKV transmission and increased frequency of mild to severe neuropathologies including microcephaly 5,6 . ZIKV was detected in the amniotic fluid of pregnant women 7 suggesting that the placenta might be permissive to virus passage. This condition likely occurs during the first trimester of pregnancy 8 , although placental cells appear to be protected against ZIKV infection by a constitutive interferon (IFN)-λ 1 response 9 . Indeed, three recent studies showed that human primary placental macrophages, trophoblasts and fibroblasts of the maternal decidua basalis were permissive to ZIKV productive infection in vitro [10][11][12] . Additional studies demonstrated that ZIKV can cross the placental barrier either via uterine vessels or by an ascending route as recently demonstrated in a mouse model of vaginal ZIKV infection 13 . Vector-independent transmission of ZIKV among humans can indeed occur through the sexual route 14 . Male-to-female transmission has been reported in approximately 15 cases thus far 15 . ZIKV sexual transmission is also supported by both the detection of higher viral load in semen vs. blood and by the persistence of ZIKV in semen for several months after waning of symptoms [16][17][18][19] . More recently, female-to-male sexual transmission of ZIKV infection was also documented 20 . These observations imply a potentially prominent role of the female reproductive tract (FRT) as a site of virus infection and propagation either from and to the male partner during

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Progress and Perspectives on HIV-1 microbicide development

Cited by 25 publications

References 190 publications

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

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