Vaginal Epithelium Transiently Harbours HIV-1 Facilitating Transmission.

Vaginal transmission accounts for majority of newly acquired HIV infections worldwide. Initial events that transpire post-viral binding to vaginal epithelium leading to productive infection in the female reproductive tract are not well elucidated. Here, we examined the interaction of HIV-1 with vaginal epithelial cells (VEC) using Vk2/E6E7, an established cell line exhibiting an HIV-binding receptor phenotype (CD4-CCR5-CD206+) similar to primary cells.

Analysis of sequence diversity and selection pressure in HIV-1 clade C gp41 from India.

Evaluation of viral diversity is critical for the rational design of treatment modalities against Human immunodeficiency virus (HIV). Predominated by HIV-1 clade C (HIV-1C), the epidemic in India represents the third largest population infected with HIV-1 globally. Glycoprotein 41 (gp41) is critical for viral replication and is a target for the design of therapeutic strategies.

Effect of diversity in gp41 membrane proximal external region of primary HIV-1 Indian subtype C sequences on interaction with broadly neutralizing antibodies 4E10 and 10E8.

Human Immunodeficiency Virus-1 Clade C (HIV-1C) dominates the AIDS epidemic in India, afflicting 2.1 million individuals within the country and more than 15 million people worldwide. Membrane proximal external region (MPER) is an attractive target for broadly neutralizing antibody (bNAb) based therapies.

Membrane-initiated estrogen signaling in prostate cancer: A route to epithelial-to-mesenchymal transition.

The plasma membrane (PM) is considered as a major druggable site. More than 50% of the existing drugs target PM proteins. In the wake of emerging data indicating a key role of estrogens in prostate cancer (PCa) pathogenesis, the study was undertaken to explore whether the estrogen binding sites exist on the PM and if such sites are functionally relevant in PCa.

Evaluation of Phytopolyphenols for their gp120-CD4 Binding Inhibitory Properties by In Silico Molecular Modelling & In Vitro Cell Line Studies.

Background: Lack of effective early-stage HIV-1 inhibitor instigated the need for screening of novel gp120-CD4 binding inhibitor. Polyphenols, a secondary metabolite derived from natural sources are reported to have broad spectrum HIV-1 inhibitory activity. However, the gp120-CD4 binding inhibitory activity of polyphenols has not been analysed in silico yet.

Tetrahydrocurcumin-loaded vaginal nanomicrobicide for prophylaxis of HIV/AIDS: in silico study, formulation development, and in vitro evaluation.

A vaginal microbicide is a front-line women-dependent approach and an alternative to a condom for prevention of unprotected sexual intercourse-associated HIV. The microbicide research is still in its infancy with several products in the clinical studies being reported to have good efficacy, safe, but with poor adherence. One such molecule reported with an excellent efficacy when tested preclinically is curcumin, a natural polyphenol derived from Curcuma longa.

Immunogenicity of virus-like Semliki Forest virus replicon particles expressing Indian HIV-1C gag, env and polRT genes.

Development of a vaccine targeting human immunodeficiency virus-1 subtype C (HIV-1C) is an important public health priority in regions with a high prevalence of the clade C virus. The present study demonstrates the immunogenicity of recombinant Semliki Forest virus (SFV)-based virus-like replicon particles (VRPs) expressing Indian HIV-1C env/gag/polRT genes. Immunization of mice with recombinant VRPs in a homologous prime-boost protocol, either individually or in combination, elicited significant antigen-specific IFN-γ T cell responses as detected by the ELISPOT assay.

Current status of a unique vaccine preventing pregnancy.

The ability of a vaccine linking beta hCG to a carrier to generate antibodies against hCG, its reversibility and safety was established by Phase I clinical trials conducted in India, Finland, Sweden, Chile and Brazil. Employing a hetero-species dimer (beta hCG-αoLH) linked to tetanus toxoid further improved the immunogenicity of the vaccine. Phase II clinical trials showed that anti-hCG titres above 50 ng/ml prevented pregnancy of sexually active fertile women without derangement of ovulation and menstrual regularity.

Nevirapine Loaded Core Shell Gold Nanoparticles by Double Emulsion Solvent Evaporation: In vitro and In vivo Evaluation.

Background: HIV/AIDS is a macrophage resident infection localized in the reticuloendothelial system and remote locations of brain and bone marrow. We present core shell nanoparticles of gold(AuNPs) and nevirapine(NVP) for targeted delivery to the multiple HIV reservoirs. The aim of the study was to design core shell NVP loaded AuNPs with high drug loading and to evaluate biodistribution of the nanoparticles in possible HIV reservoirs in vivo.

In situ polyethylene sebacate particulate carriers as an alternative to Freund's adjuvant for delivery of a contraceptive peptide vaccine--A feasibility study.

The present study evaluates the feasibility of particulate carriers of a biodegradable polymer polyethylene sebacate (PES) as an alternative to Freund's adjuvant in the design of a peptide vaccine formulation. The vaccine formulation comprised of PES and the antigen KLH conjugated 80kDa HSA peptide-1 dissolved in N-methyl-2-pyrrolidone (NMP)/NMP-water as solvent. The antigen revealed good stability and the formulations were readily syringeable.

Immunogenicity of Semliki Forest virus based self-amplifying RNA expressing Indian HIV-1C genes in mice.

Development of recombinant vaccines is considered as a promising approach to prevent transmission and eradication of HIV/AIDS. Candidate vaccines tested so far have shown poor to modest efficacy. Self-amplifying RNAs of positive strand alphaviruses are reported to be promising vectors for development of recombinant vaccines.

Advances in development of a contraceptive vaccine against human chorionic gonadotropin.

Introduction: There is continuing need for contraceptives. According to World Health Organization, 210 million pregnancies occur each year, out of which some 80 million are unintended. A vaccine offering privacy and periodic intake would be an attractive proposition.

Evaluation of cystatin C activities against HIV.

Background & Objectives: Several host defense proteins known to possess antimicrobial activities are present on mucosal surfaces and are consequently found in body fluids of vertebrates. Naturally occurring protease inhibitors like cystatins, especially cystatin C (cys C), are abundantly present in human seminal plasma. Although its antiviral activity against herpes simplex virus (HSV) has been demonstrated, the role of this protein against HIV is not well studied.

Development of antifertility vaccine using sperm specific proteins.

Sperm proteins are known to be associated with normal fertilization as auto- or iso-antibodies to these proteins may cause infertility. Therefore, sperm proteins have been considered to be the potential candidate for the development of antifertility vaccine. Some of the sperm proteins proved to be promising antigens for contraceptive vaccine includes lactate dehydrogenase (LDH-C4), protein hyaluronidase (PH-20), and Eppin.

Evaluation of a lactogenic activity of an aqueous extract of Cyperus rotundus Linn.

Ethnopharmacological Relevance: In Ayurveda, the rhizome of Cyperus rotundus Linn has been reported for wide spectrum of biological activities including lactational therapy for increasing milk quantity. However, not a single report is available on validation of its herbal galactagogue potentiality in literature. Thus, the present study is aimed to assess the lactogenic property of aqueous extract of Cyperus rotundus (CRE).

Increased activity of goat liver plasma membrane alkaline phosphatase upon release by phosphatidylinositol-specific phospholipase C.

Mammalian alkaline phosphatase (ALP) is attached to the plasma membrane by a unique glycosylphosphatidylinositol (GPI) anchor. The influence of such a complex anchoring device on the enzyme function is not fully understood. Here, we report the effect of cleavage of the GPI anchor on the activity of goat liver plasma membrane ALP (GLPM-ALP).

Foeniculum vulgare Mill: a review of its botany, phytochemistry, pharmacology, contemporary application, and toxicology.

Foeniculum vulgare Mill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology of Foeniculum vulgare.

Traditional uses, phytochemistry and pharmacology of Ficus carica: a review.

Context: Ficus carica Linn (Moraceae) has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used in gastrointestinal tract and urinary tract infection.

Objective: This review gathers the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology of Ficus carica.

Echography of the cervix and uterus during the proliferative and secretory phases of the menstrual cycle in bonnet monkeys (Macaca radiata).

We undertook the present study to investigate the echographic characteristics of the uterus and cervix of female bonnet monkeys ( Macaca radiata ) during the proliferative and secretory phases of the menstrual cycle. The cervix was tortuous in shape and measured 2.74 ± 0.

HIV gp120 induced gene expression signatures in vaginal epithelial cells.

Gp120 is the envelope protein of HIV which binds to CD4 independent proteins on vaginal epithelial cells. HIV-gp120 has been reported to modulate gene expression in several cell types. How this interaction may alter the physiologic vaginal milieu during the earliest stages of vaginal transmission of HIV, is currently unknown.

Association of human mannose receptor in sexual transmission of human immunodeficiency virus in serodiscordant couples.

HIV binds specifically to the human mannose receptor (hMR) on vaginal epithelial cells that are devoid of a conventional CD4 receptor. HIV binding to hMR on vaginal epithelial cells induces the production of matrix metalloproteinase 9 (MMP9) leading to degradation of the extracellular matrix, which may increase the risk of HIV entry into vaginal epithelial cells and further transmission into distal cells. Immunofluorescent localization of hMR on vaginal epithelial cells of seronegative females from the general population included the control group (n=52) and seronegative females from serodiscordant couples.

HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces production of matrix metalloproteinases.

Background: During sexual transmission of HIV in women, the virus breaches the multi-layered CD4 negative stratified squamous epithelial barrier of the vagina, to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have previously reported human mannose receptor (hMR) as a CD4 independent receptor playing a role in HIV transmission on human spermatozoa.

Possible transmission of HIV Infection due to human bite.

The potential risk of HIV-1 infection following human bite although epidemiologically insignificant, but it is biologically possible. There are anecdotal reports of HIV transmission by human bites particularly if saliva is mixed with blood. The oral tissues support HIV replication and may serve as a previously unrecognized HIV reservoir.

Characterization of human immunodeficiency virus (HIV1C) variants in peripheral blood mononuclear cells and spermatozoa.

The presence of distinct viral variants in different cells and secretions of the same person influences the transmission of HIV as well as the response to the host defense and to therapy. Sperm-associated virus is also a risk factor for sexual transmission of HIV. Characterization of the C2-V3 region of HIV1C env gene by the Heteroduplex Mobility Assay (HMA) and sequencing demonstrated the presence of distinct variants in the peripheral blood mononuclear cells (PBMCs) and the sperm of the same individual (n = 6).

Differential pathogenicity of SHIV infection in pig-tailed and rhesus macaques.

Background: Differential pathogenicity has been observed in cynomolgus and rhesus macaques following primate lentivirus infection. However, little is known about the comparative susceptibility of pig-tailed macaques to lentivirus infection and diseases.

Methods: We compared the in vivo infectivity and pathogenicity of a CCR5-tropic SHIV(SF162 P4) after intravenous, intravaginal or intrarectal inoculation in rhesus and pig-tailed macaques.