Influence of IL-6, IL-8, and TGF-β 1 gene polymorphisms on the risk of human papillomavirus-infection in women from Pernambuco, Brazil

Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus.

Host genomic HIV restriction factors modulate the response to dendritic cell-based treatment against HIV-1.

Host genome is still poorly investigated in the context of vaccine or immunotherapy, however recently findings emphasized that it may affect the response to those treatments. In our retrospective study we evaluated the effect of HIV-1 genetic restriction factors on the response to dendritic cell (DC)-based immunotherapy in a Brazilian cohort of HIV positive (HIV+) patients that underwent a phase I clinical trial in 2004. Genomic DNA from 18 HIV+ individuals that underwent DC-based immunotherapy was analyzed for selected polymorphisms known to be associated with susceptibility to HIV-1 infection and/or AIDS progression. Allelic and genotypic distribution of the 22 polymorphisms was evaluated considering the response to the treatment. The rs11884476 SNP in PARD3B resulted associated with good response to immune treatment according to an over-dominant model. Even if functional effect of this variation is still unknown, our data suggested that it could play a role in the control of viral replication. Our findings, being aware of the limitation represented by the small number of subjects analyzed, suggest that genetic factors involved in AIDS progression could affect the response to immunotherapy, reinforcing the idea that deeper investigation on host genetic variations will be fundamental for a rational vaccine development.

HIV mother-to-child transmission: a complex genetic puzzle tackled by Brazil and Argentina research teams.

Human immunodeficiency virus (HIV) mother-to-child transmission is a complex event, depending upon environmental factors and is affected by host genetic factors from mother and child, as well as viral genetic elements. The integration of multiple parameters (CD4 cell count, virus load, HIV subtype, and host genetic markers) could account for the susceptibility to HIV infection, a multifactorial trait. The goal of this manuscript is to analyze the immunogenetic factors associated to HIV mother-to-child transmission, trying to unravel the genetic puzzle of HIV mother-to-child transmission and considering the experience in this topic of two research groups from Brazil and Argentina.

Molecular characterization of SINES integrated in endogenous retrovirus sequences from Leopardus geoffroyi and Puma concolor / Molecular characterization of SINES integrated in endogenous retrovirus sequences from Leopardus geoffroyi and Puma concolor

Background: Short interspersed nuclear elements (SINEs) are transposable elements which are transcribed by RNA polymerase III and widespread in mammalian genomes. Can-SINE is a family of SINE sequences specific to carnivores, predominant in their genomes and present in high copy numbers. The aim of this study was to characterize sequences of Can-SINEs integrated into sequences of endogenous retroviruses (ERVs) from Brazilian wild cats Puma concolor and Leopardus geoffroyi. Additionally, these sequences are considered from some perspectives of their evolution. Material, Methods and Results: By using PCR and sequencing to screen for ERVs within the genomes of L. geoffroyi and P. concolor, two new ERV sequences were amplified with an insertion around 220 nucleotides long, similar to published carnivore SINEs. The sequences were further identified and characterized using a combination of BLAST, BLAT searches and phylogenetic analyses. The results showed that SINE sequences integrated into the ERV from P. concolor (SINE_Pco) and L. geoffroyi (SINE_Lg) are lysine-tRNA derived. These sequences presented a typical RNA polymerase III-specific internal promoter sequence followed by a microsatellite region (TC)n and by an A/T-rich tail with the polyadenylation signal AATAAA. BLAST searches using the whole sequence of L. geoffroyi clone as query (ERV plus SINE) detected two sequences which

Background: Short interspersed nuclear elements (SINEs) are transposable elements which are transcribed by RNA polymerase III and widespread in mammalian genomes. Can-SINE is a family of SINE sequences specific to carnivores, predominant in their genomes and present in high copy numbers. The aim of this study was to characterize sequences of Can-SINEs integrated into sequences of endogenous retroviruses (ERVs) from Brazilian wild cats Puma concolor and Leopardus geoffroyi. Additionally, these sequences are considered from some perspectives of their evolution. Material, Methods and Results: By using PCR and sequencing to screen for ERVs within the genomes of L. geoffroyi and P. concolor, two new ERV sequences were amplified with an insertion around 220 nucleotides long, similar to published carnivore SINEs. The sequences were further identified and characterized using a combination of BLAST, BLAT searches and phylogenetic analyses. The results showed that SINE sequences integrated into the ERV from P. concolor (SINE_Pco) and L. geoffroyi (SINE_Lg) are lysine-tRNA derived. These sequences presented a typical RNA polymerase III-specific internal promoter sequence followed by a microsatellite region (TC)n and by an A/T-rich tail with the polyadenylation signal AATAAA. BLAST searches using the whole sequence of L. geoffroyi clone as query (ERV plus SINE) detected two sequences which

Molecular characterization of SINEs integrated in endogenous retrovirus sequences from Leopardus geoffroyi and Puma concolor

Background: Short interspersed nuclear elements (SINEs) are transposable elements which are transcribed by RNA polymerase III and widespread in mammalian genomes. Can-SINE is a family of SINE sequences specific to carnivores, predominant in their genomes and present in high copy numbers. The aim of this study was to characterize sequences of Can-SINEs integrated into sequences of endogenous retroviruses (ERVs) from Brazilian wild cats Puma concolor and Leopardus geoffroyi. Additionally, these sequences are considered from some perspectives of their evolution. Material, Methods and Results: By using PCR and sequencing to screen for ERVs within the genomes of L. geoffroyi and P. concolor, two new ERV sequences were amplified with an insertion around 220 nucleotides long, similar to published carnivore SINEs. The sequences were further identified and characterized using a combination of BLAST, BLAT searches and phylogenetic analyses. The results showed that SINE sequences integrated into the ERV from P. concolor (SINE_Pco) and L. geoffroyi (SINE_Lg) are lysine-tRNA derived. These sequences presented a typical RNA polymerase III-specific internal promoter sequence followed by a microsatellite region (TC)n and by an A/T-rich tail with the polyadenylation signal AATAAA. BLAST searches using the whole sequence of L. geoffroyi clone as query (ERV plus SINE) detected two sequences which were highly similar to the cougar (P. concolor) and the domestic cat. However, the SINE from Leopardus geoffroyi is not present in these related sequences. On the other hand, during searches using the whole sequence of the P. concolor clone as query, we found the same SINE insertion in a very similar ERV from domestic cat. All insertions occurred in the RT domain, but SINE_Lg was integrated in a distinct site when compared to SINE_Pco. Another interesting difference between these SINE sequences was that the statistics reported in BLAST searches recovered a much higher number of hits from the domestic cat genome using SINE_Lg as seed than in searches for sequences related to SINE_Pco. The phylogenetic tree based on the SINE fragment grouped these new SINE sequences with Can-SINEs from felids. Within this major clade SINE_Lg and SINE_Pco are related to different lineages of felids Can-SINEs. Discussion: In this study we showed that two different sequences from felid endogenous retrovirus harbor Can-SINE sequences. These insertions are not surprising taking account that ~11% of domestic cat genome is composed of SINE sequences and they are ubiquitous in felid genomes. Furthermore, the insertions of SINEs into the ERV sequences reported here are not unique events. However, they are curious insertions representing genomic fossils and a little piece of felid history. Based on the results of the phylogenetic analyses and position of the integration sites, we suggest that SINE_Lg and SINE_Pco represent independent integration events originated by derived copies from different progenitors. We hypothesized that SINE_Lg is a "young" integration due to the absence of highly similar ERVs from Puma concolor and Felis catus. This lineage may be recently active in felid genomes given that we found very similar MegaBLAST hits at EST database from domestic cat. Instead, SINE_Pco seems to be "old", sharing an identical insertion site to ERVs from domestic cat and its lineage could be inactive in felids considering that any MegaBLAST hits resulted from EST database searches. The latter suggests an integration event in an ancestor species at least 6.7 million years ago, which represents the split between puma and domestic cat lineages.

Molecular characterization of SINES integrated in endogenous retrovirus sequences from Leopardus geoffroyi and Puma concolor / Molecular characterization of SINES integrated in endogenous retrovirus sequences from Leopardus geoffroyi and Puma concolor

Background: Short interspersed nuclear elements (SINEs) are transposable elements which are transcribed by RNA polymerase III and widespread in mammalian genomes. Can-SINE is a family of SINE sequences specific to carnivores, predominant in their genomes and present in high copy numbers. The aim of this study was to characterize sequences of Can-SINEs integrated into sequences of endogenous retroviruses (ERVs) from Brazilian wild cats Puma concolor and Leopardus geoffroyi. Additionally, these sequences are considered from some perspectives of their evolution. Material, Methods and Results: By using PCR and sequencing to screen for ERVs within the genomes of L. geoffroyi and P. concolor, two new ERV sequences were amplified with an insertion around 220 nucleotides long, similar to published carnivore SINEs. The sequences were further identified and characterized using a combination of BLAST, BLAT searches and phylogenetic analyses. The results showed that SINE sequences integrated into the ERV from P. concolor (SINE_Pco) and L. geoffroyi (SINE_Lg) are lysine-tRNA derived. These sequences presented a typical RNA polymerase III-specific internal promoter sequence followed by a microsatellite region (TC)n and by an A/T-rich tail with the polyadenylation signal AATAAA. BLAST searches using the whole sequence of L. geoffroyi clone as query (ERV plus SINE) detected two sequences which

Background: Short interspersed nuclear elements (SINEs) are transposable elements which are transcribed by RNA polymerase III and widespread in mammalian genomes. Can-SINE is a family of SINE sequences specific to carnivores, predominant in their genomes and present in high copy numbers. The aim of this study was to characterize sequences of Can-SINEs integrated into sequences of endogenous retroviruses (ERVs) from Brazilian wild cats Puma concolor and Leopardus geoffroyi. Additionally, these sequences are considered from some perspectives of their evolution. Material, Methods and Results: By using PCR and sequencing to screen for ERVs within the genomes of L. geoffroyi and P. concolor, two new ERV sequences were amplified with an insertion around 220 nucleotides long, similar to published carnivore SINEs. The sequences were further identified and characterized using a combination of BLAST, BLAT searches and phylogenetic analyses. The results showed that SINE sequences integrated into the ERV from P. concolor (SINE_Pco) and L. geoffroyi (SINE_Lg) are lysine-tRNA derived. These sequences presented a typical RNA polymerase III-specific internal promoter sequence followed by a microsatellite region (TC)n and by an A/T-rich tail with the polyadenylation signal AATAAA. BLAST searches using the whole sequence of L. geoffroyi clone as query (ERV plus SINE) detected two sequences which