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Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission.

ABSTRACT: Perforin-1, a component of the immune system, is able to control Human Immunodeficiency Virus-1 (HIV-1) replication and could be involved in HIV-1 mother-to-child transmission (MTCT). This study aims at evaluating the role of the c.900C > T PRF1 gene (encoding for perforin-1) polymorphism (rs885822) in HIV-1 MTCT. The PRF1 c.900C > T polymorphism was genotyped in 331 children from Zambia using a Taqman probe on a Real Time PCR platform. The PRF1 c.900C > T C/T genotype was more frequent among HIV-1 exposed but non-infected children than in HIV-1 positive cases, and the results were confirmed among children infected during breastfeeding. PRF1 c.900C > T correlated with protection against HIV-1 MTCT, suggesting its role in HIV-1 vertical transmission.

SUBMITTER: Zupin L

PROVIDER: S-EPMC6905447 | biostudies-literature | 2019 Jul-Sep

REPOSITORIES: biostudies-literature

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Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission.

Zupin Luisa L Polesello Vania V Kamada Anselmo Jiro AJ Gratton Rossella R Segat Ludovica L Kuhn Louise L Crovella Sergio S

Genetics and molecular biology 20190701 3

Perforin-1, a component of the immune system, is able to control Human Immunodeficiency Virus-1 (HIV-1) replication and could be involved in HIV-1 mother-to-child transmission (MTCT). This study aims at evaluating the role of the c.900C > T PRF1 gene (encoding for perforin-1) polymorphism (rs885822) in HIV-1 MTCT. The PRF1 c.900C > T polymorphism was genotyped in 331 children from Zambia using a Taqman probe on a Real Time PCR platform. The PRF1 c.900C > T C/T genotype was more frequent among HI ...[more]

PMID: 31188937

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Project description:BackgroundThe human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) plays a pivotal role in the viral lifecycle: including encapsulating the viral genome, aiding in strand transfer during reverse transcription, and packaging two copies of the viral genome into progeny virions. Another gag gene product, p6, plays an integral role in successful viral budding from the plasma membrane and inclusion of the accessory protein Vpr within newly budding virions. In this study, we have characterized the gag NC and p6 genes from six mother-infant pairs following vertical transmission by performing phylogenetic analysis and by analyzing the degree of genetic diversity, evolutionary dynamics, and conservation of functional domains.ResultsPhylogenetic analysis of 168 gag NC and p6 genes sequences revealed six separate subtrees that corresponded to each mother-infant pair, suggesting that epidemiologically linked individuals were closer to each other than epidemiologically unlinked individuals. A high frequency (92.8%) of intact open reading frames of NC and p6 with patient and pair specific sequence motifs were conserved in mother-infant pairs' sequences. Nucleotide and amino acid distances showed a lower degree of viral heterogeneity, and a low degree of estimates of genetic diversity was also found in NC and p6 sequences. The NC and p6 sequences from both mothers and infants were found to be under positive selection pressure. The two important functional motifs within NC, the zinc-finger motifs, were highly conserved in most of the sequences, as were the gag p6 Vpr binding, AIP1 and late binding domains. Several CTL recognition epitopes identified within the NC and p6 genes were found to be mostly conserved in 6 mother-infant pairs' sequences.ConclusionThese data suggest that the gag NC and p6 open reading frames and functional domains were conserved in mother-infant pairs' sequences following vertical transmission, which confirms the critical role of these gene products in the viral lifecycle.

Project description:The reverse transcriptase (RT) enzyme of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in the life cycle of the virus by converting the single stranded RNA genome into double stranded DNA that integrates into the host chromosome. In addition, RT is also responsible for the generation of mutations throughout the viral genome, including in its own sequences and is thus responsible for the generation of quasi-species in HIV-1-infected individuals. We therefore characterized the molecular properties of RT, including the conservation of functional motifs, degree of genetic diversity, and evolutionary dynamics from five mother-infant pairs following vertical transmission.The RT open reading frame was maintained with a frequency of 87.2% in five mother-infant pairs' sequences following vertical transmission. There was a low degree of viral heterogeneity and estimates of genetic diversity in mother-infant pairs' sequences. Both mothers and infants RT sequences were under positive selection pressure, as determined by the ratios of non-synonymous to synonymous substitutions. Phylogenetic analysis of 132 mother-infant RT sequences revealed distinct clusters for each mother-infant pair, suggesting that the epidemiologically linked mother-infant pairs were evolutionarily closer to each other as compared with epidemiologically unlinked mother-infant pairs. The functional domains of RT which are responsible for reverse transcription, DNA polymerization and RNase H activity were mostly conserved in the RT sequences analyzed in this study. Specifically, the active sites and domains required for primer binding, template binding, primer and template positioning and nucleotide recruitment were conserved in all mother-infant pairs' sequences.The maintenance of an intact RT open reading frame, conservation of functional domains for RT activity, preservation of several amino acid motifs in epidemiologically linked mother-infant pairs, and a low degree of genetic variability following vertical transmission is consistent with an indispensable role of RT in HIV-1 replication in infected mother-infant pairs.

Project description:BackgroundThe burden of mother-to-child transmission rate of HIV is high and risk factors are common in Ethiopia. This systematic review and meta-analysis intended to provide the pooled estimation of mother-to-child transmission rate and its risk factors in Ethiopia.MethodsWe searched PubMed, Google Scholar, EMBASE and Web of Science electronic databases for all available references. We included observational studies including case-control, cohort, and cross-sectional studies. The search was further limited to studies conducted in Ethiopia and publish in English. Heterogeneity was checked using the I2 statistic. Egger's test and the funnel plot were used to assess publication bias. A meta-analysis using a weighted inverse variance random-effects model was performed.ResultsA total of 18 studies with 6253 individuals were included in this systematic review and meta-analysis. Of these, 14 studies with 4624 individuals were used to estimate the prevalence. The estimated pooled prevalence of mother-to-child transmission of HIV was 11.4% (95% CI = 9.1-13.7). The pooled adjusted odds ratio (AOR) of mother-to-child transmission of HIV for the infants from rural area was 3.8 (95% CI = 1.4 to 6.3), infants delivered at home was 3.2 (95% CI = 1.2 to 5.2), infant didn't take antiretroviral prophylaxis was 5.8 (95% CI = 1.5 to 10.3), mother didn't take antiretroviral prophylaxis was 6.1 (95% CI = 2.5 to 9.6), mothers didn't receive PMTCT intervention was 5.1 (95% CI = 1.6, 8.6), and on mixed feeding was 4.3 (95% CI = 1.8 to 6.7).ConclusionsThis systematic review and meta-analysis showed that mother-to-child transmission rate of HIV was high in Ethiopia. Being from the rural residence, home delivery, not taking antiretroviral prophylaxis, the absence of PMTCT intervention, and mixed infant feeding practices increased the risk of HIV transmission.Trial registrationIt is registered in the Prospero database: (PROSPERO 2017: CRD42017078232 ).

Dataset Information

Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission.

Publications

Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission.

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