Association of CD209L tandem repeats polymorphism with susceptibility to human immunodeficiency virus-1 infection, disease progression, and treatment outcomes: a Moroccan cohort study (original) (raw)
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Clinical Microbiology and Infection, 2014
In order to investigate the association between length variation of the CD209L neck region and human immunodeficiency virus (HIV)-1 susceptibility, disease progression, and treatment response outcomes, we genotyped 139 HIV-1-seropositive and 109 seronegative individuals. The heterozygous genotype 6/5 showed a significant increased risk of HIV-1 infection (OR 3.03, 95% CI 0.99-9.33, p 0.046). Moreover, after highly active antiretroviral therapy (HAART), HIV-1-seropositive individuals carrying the 6/5, 7/5 and 7/7 genotypes and alleles 5, 6 and 7 showed good CD4 + T-cell recovery. In addition, individuals with the 7/5, 6/6 and 7/7 genotypes showed a significant decrease in viral load during the treatment period as compared with baseline (p < 0.05). Interestingly, we found that alleles 4 and 6 were associated with protection against AIDS progression. D209L variation may influence susceptibility to HIV-1, response to treatment, and disease progression.
Protective Role of DC‐SIGN (CD209) Neck‐Region Alleles with <5 Repeat Units in HIV‐1 Transmission
The Journal of Infectious Diseases, 2008
HIV-1 transmission, we studied 530 HIV-1-positive and 341 HIV-1-negative individuals in China. The carrier frequency of a DC-SIGN allele with <5 repeat units in the neck-region was 0.9% in HIV-1-positive and 3.8% in HIV-1negative individuals (P ؍ .007), an observation suggesting that this DC-SIGN variation plays a role in HIV-1 transmission. These naturally occurring DC-SIGN neck-region variants were significantly more frequent in the Chinese population than in the US population (P<.001) and in a worldwide population (P ؍ .006).
Aids Research and Human Retroviruses, 2009
Allelic differences of chemokine (C-C motif ) receptor 5 (CCR5) and CCR2, as well as the ligand for the chemokine receptor CXCR4, stromal-derived factor (SDF-1), are known to suppress HIV-1 transmission and to be involved in delay in HIV-1 disease progression. The aim of our study was to investigate the frequencies of four mutations that confer resistance to HIV-1: CCR5-D32, CCR5-m303, CCR2-64I, and SDF1-3 0 A among Bahrainis. We have studied the DNA polymorphisms in 304 unrelated healthy Bahraini individuals without any known history of HIV-1 infection or AIDS symptoms. The CCR5-D32 mutation was detected by PCR analysis, while the CCR5-m303, CCR2-64I, and SDF1-3 0 A mutations were detected by PCR-restriction fragment length polymorphism (PCR-RFLP) tests. Allele frequencies and the fit to the Hardy-Weinberg equilibrium were evaluated using the Arlequin population genetics application. The frequencies of the CCR5-D32, CCR2-64I, and SDF1-3 0 A alleles were 2.8%, 8.9%, and 26.5%, respectively. No mutant alleles were detected for the CCR5-m303 mutation in 304 individuals. We estimated the risk of AIDS onset (relative hazard), computed from the three-locus genotype data. This is the first report of these four mutations conferring resistance to HIV-1 in the Bahraini population. The presence of the CCR5-D32 allele among Bahrainis may be attributed to the admixture with people of European descent. The CCR2-64I allele and especially the SDF1-3 0 A allele are predominant in the Bahraini population and may be associated with resistance to fast HIV-1 infection in Bahrainis, and thus their genotyping can be used for prognosis in HIV-infected individuals.
Gene Reports, 2020
Background: Several studies have reported that the CCR2-64I genetic polymorphism influences the rate of markers of HIV-1 disease progression (HIV-1 viral loads and CD4+ T cell counts). However, the association between this mutation and HIV-1 infection among antiretroviral therapy (ART)-treated HIV-1 seropositive patients is controversial. In Morocco, no data is available regarding this polymorphism. Objectives: In the present case-control study, we aimed to investigate the frequency of the CCR2-64I genetic polymorphism and to evaluate the association of this mutant allele with susceptibility to HIV-1 infection and immunovirological outcomes in Morocco. Methods: We recruited 100 HIV-1 seropositive patients (cases) undergoing antiretroviral therapy (ART) and 200 HIV-1 seronegative individuals from Mohammed V Military Training Hospital in Rabat. Genotyping of the CCR2-64I polymorphism was performed using Polymerase Chain Reaction (PCR) assay and automated DNA sequencing. The comparison between variables was performed using χ2-test, Fisher's exact test, or Mann-Whitney U test, as appropriate. Factors associated with immunovirological outcomes were assessed using logistic regression analysis. Results: The frequencies of CCR2-64V/CCR2-64V, CCR2-64V/CCR2-64I and CCR2-64I/CCR2-64I genotypes were 67, 30 and 3%, respectively among HIV-1 infected patients (cases), compared to 73, 24.50, and 2.50%, respectively, among HIV-1 uninfected individuals (controls). We didn't observe any statistically significant difference in the genotype distribution between cases and control groups. Additionally, the multivariate logistic regression analysis didn't reveal a significant association between the CCR2-64I polymorphism and the immunovirological outcomes after one year of ART (p > 0.05). Conclusion: We are the first to report the frequency of CCR2-64I polymorphism and its association with HIV-1 infection in Moroccan individuals. Our findings suggest that the CCR2-64I allele may not influence the susceptibility to HIV-1 infection, as was previously reported in other populations. Besides, we hypothesize that this mutation, independently of classical risk factors, may not impact the virological outcomes and immunological
Journal of Clinical Immunology, 2007
Despite multiple sexual exposures to HIV-1 virus, some individuals remain HIV-1 seronegative. Although several genetic factors have been related to HIV-1 resistance, the homozygosity for a mutation in CCR5 gene (the 32-bp deletion, i.e., CCR5-Delta32 allele) is presently considered the most relevant one. The C-type lectins, DC-SIGN (present on dendritic cells and macrophages) and DC-SIGNR (present on endothelial cells in liver and lymph nodes) efficiently bind and transmit HIV-1 to susceptible cell in trans, thereby augmenting the infection. A potential association of the DC-SIGN and DC-SIGNR neck domain repeat polymorphism and risk of HIV-1 infection is currently under debate. To determine the influence of host genetic factors on HIV-1 resistance, we conducted genetic risk association study in HIV-1-exposed seronegative (n=47) individuals, HIV-1 seronegative (n=262) healthy control, and HIV-1-infected seropositive patients (n=168) for polymorphism in neck domain of DC-SIGN and DC-SIGNR genes. The DC-SIGN and DC-SIGNR genotypes were identified by polymerase chain reaction method in DNA extracted from peripheral blood and confirmed by sequencing. Fisher exact or χ 2 test was used for static analysis. DC-SIGN genotype and allele distribution was fairly similar in HIV-1-exposed seronegative, HIV-1 seropositive, and HIV-1 seronegative control. There was no statistical significance in the differences in the distribution of DC-SIGN genotypes. A total of 13 genotypes were found in DC-SIGNR neck repeat region polymorphism. Among all the genotypes, only 5/5 homozygous showed significant reduced risk of HIV-1 infection in HIV-1exposed seronegative individuals (p=0.009). A unique genotype 8/5 heterozygous was also found in HIV-1 seropositive individual, which is not reported elsewhere.
Journal of Virology, 2006
Tumor susceptibility gene 101 (TSG101) encodes a host cellular protein that is appropriated by human immunodeficiency virus type 1 (HIV-1) in the budding process of viral particles from infected cells. Variation in the coding or noncoding regions of the gene could potentially affect the degree of TSG101-mediated release of viral particles. While the coding regions of the gene were found to lack nonsynonymous variants, two polymorphic sites in the TSG101 5 area were identified that were associated with the rate of AIDS progression among Caucasians. These single-nucleotide polymorphisms (SNPs), located at positions ؊183 and ؉181 relative to the translation start, specify three haplotypes termed A, B, and C, which occur at frequencies of 67%, 21%, and 12%, respectively. Haplotype C is associated with relatively rapid AIDS progression, while haplotype B is associated with slower disease progression. Both effects were dominant over the intermediate haplotype A. The haplotypes also demonstrated parallel effects on the rate of CD4 T-cell depletion and viral load increase over time, as well as a possible influence on HIV-1 infection. The data raise the hypothesis that noncoding variation in TSG101 affects the efficiency of TSG101-mediated release of viral particles from infected cells, thereby altering levels of plasma viral load and subsequent disease progression.
AIDS research and human retroviruses, 2015
Studying the genetic diversity and natural polymorphisms of HIV-1 would benefit our understanding of HIV drug resistance (HIVDR) development and predict treatment outcomes. In this study, we have characterized the HIV-1 genetic diversity and natural polymorphisms at the 5' region of pol gene encompassing the protease (PR) and reverse transcriptase (RT) from 271 plasma specimens collected in 2008 from HIV-1-infected patients who were eligible for initiating antiretroviral therapy in Abuja (Nigeria). The analysis indicated that the predominant subtype was subtype G (31.0%), followed by CRF02-AG (19.2 %), CRF43-02G (18.5%), A/CRF36-cpx (11.4%) and the remaining (19.9%) were other subtypes and circulating (CRF) and unique (URF) recombinant forms. Recombinant viruses (68.6%) were the major viral strains in the region. Eighty-four subtype G sequences were further classified into two major and two minor clusters; sequences in the two major clusters were closely related to the HIV-1 str...
BMC Infectious Diseases, 2014
Background: Despite the increasing use of antiretroviral treatment (ART) recent data on frequency and pattern of drug resistance mutations in Ethiopia is not available. Furthermore with increasing mobility of people HIV-1 subtypes other than the predominant subtype C may likely be introduced from the neighbouring countries. This study was aimed to determine the molecular characterization and pre-antiretroviral treatment resistance mutations among HIV-1 chronically infected ART naïve patients after the roll out of ART in Ethiopia. Methods: Viral RNA was determined in 160 baseline plasma samples. The entire PR and the first 335 codons (76%) of the RT regions of the pol gene of the HIV-1 genome (N = 160) were amplified and sequenced using an in-house assay. Genotypic drug resistance was defined as the presence of one or more resistance-related mutations as specified by the consensus mutation of Stanford University HIVDB and the International Antiviral Society (IAS) mutation lists. Results: A predominance of HIV-1 subtype C (98.7%) was observed. The level of drug resistance is found to be 5.6% and 13.1% according to the Stanford University HIVDB drug resistance interpretation algorithms and the International Antiviral Society mutation lists, respectively. Mutations conferring simultaneous resistance to NRTIs and NNRTIs were not detected and no major PR mutation was found. However, a high rate of polymorphic changes both in PR and RT regions were observed. Moreover, twenty four (15%) monophyletic transmission clusters with bootstrap value of 99% were found. Conclusions: Strong evidence for consistent HIV-1C clade homogeneity and low influx of other variant into the country was found. The level of drug resistance observed in chronically infected treatment naïve patients which exceeds the WHO estimates suggests the need for incorporation of HIV-1 drug resistance testing prior to ART initiation. The occurrence of monophyletic transmission clusters affecting (24/160) individuals indicates their potential risk related practice. Thus, an intensified public health intervention program and monitoring of HIV drug resistance testing appears indispensible.