A5075961091- Herpesvirus Infections and Treatments
- Reproductive tract infections research
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Poxvirus research and outbreaks
- Toxin Mechanisms and Immunotoxins
- interferon and immune responses
- HIV/AIDS Research and Interventions
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis B Virus Studies
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Cell Adhesion Molecules Research
- Vector-Borne Animal Diseases
- Systemic Lupus Erythematosus Research
- RNA regulation and disease
- Antimicrobial Peptides and Activities
- Transgenic Plants and Applications
- Virology and Viral Diseases
- Long-Term Effects of COVID-19
- Biochemical and Structural Characterization
- Cancer Mechanisms and Therapy
Albert Einstein College of Medicine
2010-2023
Children's Hospital at Montefiore
2020
Pediatrics and Genetics
2005-2018
Icahn School of Medicine at Mount Sinai
2001-2008
Mount Sinai Medical Center
2004
State Research Center of Virology and Biotechnology VECTOR
1990-1993
Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, even among those the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate antiviral immune response. We compared cytokine, humoral, cellular responses pediatric (children youth, age <24 years) (n = 65) adult 60) patients 2019...
ABSTRACT We tested the ability of 20 synthetic θ defensins to protect cells from infection by type 1 and 2 herpes simplex viruses (HSV-1 -2, respectively). The peptides included rhesus (RTDs) 3, originally isolated macaque leukocytes, three (retrocyclins 3) whose sequences were inferred human θ-defensin (DEFT) pseudogenes. also 14 retrocyclin analogues, including retro, enantio, retroenantio forms 1. Retrocyclins RTD 3 protected cervical epithelial both HSV serotypes, but only did so without...
Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion gD-2 unmasks protective antigens, we evaluated efficacy and safety an virus deleted in complemented allowing a single round replication on cells expressing HSV-1 gD (ΔgD−/+gD−1). Subcutaneous immunization C57BL/6 or BALB/c mice with ΔgD−/+gD1 provided 100% protection against lethal intravaginal skin challenges prevented latency. elicited no...
The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, effects on intracellular calcium concentration ([Ca2+]i) after exposure cells to were examined. Exposure results in a rapid and transient increase [Ca2+]i. Pretreatment with pharmacological agents block release inositol 1,4,5-triphosphate (IP3)-sensitive endoplasmic reticulum stores abrogates response. Moreover,...
Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective this study was to examine effect 14 daily applications 0.5% PRO 2000 placebo gel on immunity and intrinsic antimicrobial activity.A randomized, prospective, double-blind, placebo-controlled conducted among 24 healthy, abstinent women. Levels cytokines, chemokines, defensins, other protective factors activity were determined in cervicovaginal lavage...
The lack of biomarkers that are predictive safety is a critical gap in the development microbicides. present experiments were designed to evaluate value vitro models microbicide safety.Changes epithelial barrier evaluated by measuring transepithelial electrical resistance (TER) after exposure human cells candidate microbicides dual-chamber system. significance observed changes was addressed challenging cultures with immunodeficiency virus (HIV) and ability cross epithelium infect target T...
HSV triggers intracellular calcium release to promote viral entry. We hypothesized that Akt signaling induces the responses and contributes Exposure of human cervical primary genital tract epithelial, neuronal, or keratinocyte cells serotype 2 resulted in rapid phosphorylation Akt. Silencing with small interfering RNA prevented responses, blocked entry, inhibited plaque formation by 90% compared control siRNA. Susceptibility infection was partially restored if reintroduced into silenced an...
Rabbit neutrophil peptide-1 (NP-1), a prototypic alpha-defensin, protects cells in vitro from infection by clinical and laboratory isolates of herpes simplex virus type 2 (HSV-2). Incubation concentrated stocks for 1 h with noncytotoxic concentrations NP-1 reduces subsequent >98%. Pretreating prior to inoculation untreated also prevents infection. NP-1, cationic peptide, does not compete viral envelope glycoproteins binding cellular heparan sulfate receptors, but it entry. No VP16, major...
ABSTRACT Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes simplex (HSV) bind heparan sulfate provided rationale for development sulfated or sulfonated polymers as topical agents. Although several have advanced clinical trials, spectrum mechanism anti-HSV activity effects...
BackgroundMicrobicides used to prevent the transmission of human immunodeficiency virus (HIV) are advancing clinical trials on basis activity observed in vitro and animal models. However, no data demonstrate microbicides after application humans. This study was designed determine antiviral cervicovaginal lavage (CVL) samples collected intravaginal 0.5% PRO 2000 gel (Indevus) MethodsA randomized, double-blind conducted assess anti-HIV anti–herpes simplex (HSV) CVL obtained at screening (48...
The objective of this study was to test the activity microbicides against herpes simplex virus type 2 (HSV-2) introduced in seminal plasma. We found that plasma interfered with PRO 2000 and cellulose sulfate, increasing by 100-fold concentration drug required inhibit 90% viral plaque formation. Seminal competitively inhibited binding HSV-2 envelope. Most interference a high molecular-weight fraction; tandem mass spectrometry identified proteins as fibronectin-1 lactoferrin. In murine model,...
Secretory leukocyte protease inhibitor (SLPI), an anti-inflammatory mediator of mucosal immunity, inhibits human immunodeficiency virus (HIV) and herpes simplex (HSV) in cell culture. Epidemiological studies demonstrate that higher concentrations SLPI secretions are associated with a reduced risk HIV transmission. The current were designed to test the hypothesis HSV triggers loss evade innate immunity this response may contribute increased infection setting infection. Exposure cervical...
Herpes simplex virus (HSV) entry requires multiple interactions at the cell surface and activation of a complex calcium signaling cascade. Previous studies demonstrated that integrins participate in this process, but their precise role has not been determined. These were designed to test hypothesis integrin αvβ3 promotes release intracellular (Ca2+) stores contributes viral cell-to-cell spread. Transfection cells with small interfering RNA (siRNA) targeting αvβ3, other subunits, or treatment...
Defining and preserving the innate antiviral activity found in cervicovaginal secretions is critical. Cervicovaginal lavage (CVL) samples were obtained from 20 healthy women evaluated for anti–herpes simplex virus (HSV) activity. CVL reduced HSV-2 yields by 23-fold (median), anti-HSV of correlated with concentration human neutrophil peptides (HNP)–1–3. Both HNP-1–3 interacted prevented entry after binding. Substantially less protective was observed immunodeficiency virus—infected subjects,...
Heparan sulfate moieties serve as receptors for initial binding of herpes simplex virus types 1 and 2 (HSV-1 -2) to cells. Deletion HSV-1 glycoprotein C (gC-1) but not HSV-2 gC (gC-2) results in virions with reduced specific activity (virus particles bound per cell) infectivity (p.f.u. particle), suggesting that HSV-1, HSV-2, plays a major role mediating attachment. To test the hypothesis B (gB), other heparin-binding glycoprotein, mediates attachment, viruses deleted gB-2 alone or both gC-2...
Herpes simplex viruses (HSV) harness cellular calcium signaling pathways to facilitate viral entry. Confocal microscopy and small interfering RNA (siRNA) were used identify the source of dissect requisite viral-cell interactions. Binding HSV human epithelial cells induced no response, but shifting temperatures permissive for penetration triggered increases in plasma membrane followed by a global release intracellular calcium. Transfection with siRNA targeting proteoglycan syndecan-2 blocked...
Herpes simplex virus (HSV) entry is associated with Akt translocation to the outer leaflet of plasma membrane promote a complex signaling cascade. We hypothesized that phospholipid scramblase-1 (PLSCR1), calcium responsive enzyme flips phosphatidylserines between leaflets, might redistribute outside during entry. Confocal imaging, biotinylation proteins and flow cytometric analysis demonstrated HSV activates PLSCR1 shortly following HSV-1 or HSV-2 exposure. Translocation was blocked by...
Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites replication increase peripheral blood. We hypothesized that induces changes these facilitate reactivation tested this hypothesis human 2D10 cells, a model latency. promoted latency reversal HSV-2-infected bystander cells. Bulk single-cell RNA-Seq studies...
ABSTRACT Presently marketed vaginal barrier methods are cytotoxic and damaging to the epithelium natural flora when used frequently. Novel noncytotoxic agents needed protect men women from sexually transmitted diseases. One novel candidate is a mandelic acid condensation polymer, designated SAMMA. The spectrum mechanism of antiviral activity were explored using clinical isolates laboratory-adapted strains human immunodeficiency virus (HIV) herpes simplex (HSV). SAMMA highly effective against...
The acidic vaginal milieu is presumed to inactivate pathogens but neutralized by semen. This notion fostered the development of acid-buffering products, such as ACIDFORM (developed Program for Topical Prevention Conception and Disease, Rush University, licensed Instead), microbicides. However, extent mechanism protective activity provided buffering gels not known. Exposure herpes simplex virus (HSV) pH 4.5 or lower irreversibly inactivated HSV reduced yields at least 90%; exposure 5.0 had...
Intravaginal rings releasing tenofovir (TFV) or its prodrug, disoproxil fumarate (TDF), are being evaluated for HIV and herpes simplex virus (HSV) prevention. The current studies were designed to determine the mechanisms of drug accumulation in human vaginal immune cells. exposure epithelial T cells equimolar concentrations radiolabeled TDF resulted over 10-fold higher intracellular levels than TFV. Permeability demonstrated that TDF, but not TFV, entered by passive diffusion. uptake was...
Tenofovir gel and dapivirine ring provided variable HIV protection in clinical trials, reflecting poor adherence possibly biological factors. We hypothesized that vaginal microbiota modulates pharmacokinetics tested the effects of pH, individual bacteria, swabs from women on antiviral activity. Tenofovir, but not dapivirine, uptake by human cells was reduced as pH increased. Lactobacillus crispatus actively transported tenofovir leading to a loss drug bioavailability culture supernatants...