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Chaudhary O.,All India Institute of Medical Sciences | Bala M.,All India Institute of Medical Sciences | Bala M.,Regional Teaching Training and Research Center | Singh J.,All India Institute of Medical Sciences | And 5 more authors.
Annals of Biology | Year: 2014

Dendritic cells are professional antigen presenting cells that capture HIV-1 through DC-SIGN/DC-SIGNR. The repeat region polymorphism in the neck region of DC-SIGNR affects HIV-1 infection. This study aims at determining the frequency distribution of DC-SIGNR repeat region polymorphism in injecting drug users, patients infected with HIV-1 and healthy seronegative individuals and correlate with virological and immunological parameters. Blood from 100 healthy individuals, 100 injecting drug users and 100 patients infected with HIV-1 was collected. The repeat region polymorphism in DC-SIGNR was assessed by polymerase chain reaction. The frequency of heterozygous DC-SIGNR 7/5 genotype was significantly higher in injecting drug users, whereas the frequency of homozygous DC-SIGNR 7/7 genotype was significantly higher in patients infected with HIV-1. The heterozygosity (DC-SIGNR genotype 7/5) was associated significantly with high CD4+ T-cell count and low viral load compared to the homozygous DC-SIGNR 7/7 genotype in patients infected with HIV-1. A significantly high frequency of heterozygous DC-SIGNR genotype 7/5 in injecting drug users and its association with high CD4+T-cell count and low viral load in patients infected with HIV-1 suseests the protective role of this eenotvoe in HIV-1 infection.

Kulkarni S.,National Dairy Research Institute | Bala M.,Regional Teaching Training and Research Center | Sane S.,National Dairy Research Institute | Pandey S.,National Dairy Research Institute | And 2 more authors.
International Journal of Antimicrobial Agents | Year: 2012

A dramatic increase in the number of quinolone-resistant Neisseria gonorrhoeae isolates in India and worldwide has been reported recently. This study was undertaken to identify and characterise mutations in the gyrA and parC genes of N. gonorrhoeae resistant to six different quinolone antibiotics. In total, 64 N. gonorrhoeae clinical isolates were obtained during 2007-2009 from patients attending sexually transmitted diseases clinics (New Delhi, 35; Pune, 16; Mumbai, 6; Hyderabad, 6; and Nagpur, 1). Antimicrobial susceptibility was determined by Etest and mutation patterns in gyrA and parC were determined by sequencing analysis. All strains showed varying resistance to different quinolone analogues, ranging from 17.2% (gatifloxacin) to 98.4% (ofloxacin and norfloxacin). Sequencing of gyrA and parC revealed that 100% of strains showed mutations in gyrA and 46.9% showed mutations both in gyrA and parC. All strains showed single or double mutations at Ser-91 → Phe, Ser-91 → Thr and Asp-95 → Gly/Asn in gyrA and at Glu-91 → Gly in parC. Asp-95 → Asn mutation was the most prevalent in strains isolated from New Delhi, whilst Asp-95 → Gly was prevalent in strains isolated from Pune. Strains were categorised into eight different mutation patterns. Resistant strains with high minimum inhibitory concentrations (≥8 μg/mL) showed mutations both in gyrA and parC. The difference in the proportion of strains showing mutations in gyrA and parC was found to be significant (P < 0.001). The mutation Asp-95 → Asn was restricted to Pune strains only. These results indicate that mutations in quinolone target enzymes may have resulted in the high-level resistance seen in these isolates. © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Andrabi R.,All India Institute of Medical Sciences | Bala M.,Regional Teaching Training and Research Center | Kumar R.,All India Institute of Medical Sciences | Wig N.,All India Institute of Medical Sciences | And 2 more authors.
PLoS ONE | Year: 2012

Broadly cross neutralizing antibodies (NAbs) are generated in a group of HIV-1 infected individuals during the natural infection, but little is known about their prevalence in patients infected with viral subtypes from different geographical regions. We tested here the neutralizing efficiency of plasma antibodies from 80 HIV-1 infected antiretroviral drug naive patients against a panel of subtype-B and C tier 2 viruses. We detected cross-neutralizing antibodies in approximately 19-27% of the plasma, however the subtype-C specific neutralization efficiency predominated (p = 0.004). The neutralizing activity was shown to be exclusively mediated by the immunoglobulin G (IgG) fraction in the representative plasma samples. Epitope mapping of three, the most cross-neutralizing plasma (CNP) AIIMS206, AIIMS239 and AIIMS249 with consensus-C overlapping envelope peptides revealed ten different binding specificities with only V3 and IDR being common. The V3 and IDR were highly antigenic regions but no correlation between their reciprocal Max50 binding titers and neutralization was observed. In addition, the neutralizing activity of CNP was not substantially reduced by V3 and gp41 peptides except a modest contribution of MPER peptide. The MPER was rarely recognized by plasma antibodies though antibody depletion and competition experiments demonstrated MPER dependent neutralization in two out of three CNP. Interestingly, the binding specificity of one of the CNP (AIIMS206) overlapped with broadly neutralizing mAb 2F5 epitope. Overall, the data suggest that, despite the low immunogenicity of HIV-1 MPER, the antibodies directed to this region may serve as crucial reagents for HIV-1 vaccine design. © 2012 Andrabi et al.

Patel A.L.,University of Delhi | Chaudhry U.,University of Delhi | Sachdev D.,University of Delhi | Sachdeva P.N.,University of Delhi | And 2 more authors.
Indian Journal of Medical Research | Year: 2011

Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea.

Chaudhary O.,All India Institute of Medical Sciences | Kumar S.,All India Institute of Medical Sciences | Bala M.,Regional Teaching Training and Research Center | Singh J.,Kurukshetra University | And 2 more authors.
Viral Immunology | Year: 2015

Dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin related molecule (DC-SIGNR) is a C-type lectin, calcium-dependent carbohydrate-binding protein, which can act as a cell-adhesion and pathogen recognition receptor. DC-SIGNR is known to be highly expressed on liver sinusoidal cells and in the lymph nodes. However, its expression in peripheral blood mononuclear cells (PBMCs) in HIV-1 infection has not been addressed. Therefore, this study determined the expression of DC-SIGNR in PBMCs of HIV-1-infected patients and healthy seronegative individuals by real-time polymerase chain reaction and assessed its correlation with CD4+ T cell counts and DC-SIGNR genotypes. A significantly higher expression of DC-SIGNR was observed in the PBMCs of HIV-1-infected patients compared with healthy seronegative individuals. Further, there was a negative correlation between DC-SIGNR expression and CD4+ T cell counts and positive with viral load, with higher DC-SIGNR expression in the PBMCs of HIV-1-infected patients with a CD4+ T cell count <200 cells/μL than those with >200 cells/μL. This is the first study to report the expression of DC-SIGNR in PBMCs of HIV-1-infected patients. A salient finding of this study is that the DC-SIGNR expression was higher in HIV-1-infected patients, and its positive correlation with viral load and negative with CD4+ T cells counts suggesting a potential role of DC-SIGNR in HIV-1 infection. © Copyright 2015, Mary Ann Liebert, Inc. 2015.

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