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Envelope Gene (envelope + gene)
Selected AbstractsHepatitis C virus quasispecies in the natural course of HCV-related disease in patients with haemophiliaHAEMOPHILIA, Issue 1 2004G. Tagariello Summary., Patients with haemophilia show high prevalence of hepatitis C infection but low rate of progressive liver disease when they are not co-infected with HIV. The balance between host immune system and hepatitis C virus (HCV) variability seems to play a major role in the evolution of the HCV-related disease. To address this point we have studied, in a group of selected patients with haemophilia, the composition and in some cases the evolution, of the highest variable envelope gene within the hypervariable region 1 (HVR1) of the HCV, which is the region more directly exposed to the host immune response. Five of 12 patients show a very high homogeneity of the HVR1 and four of those had severe progressive liver disease. These results seem to confirm the major role of the immunity in driving the variability of the HCV rather than the high degree of different HCV strains to which haemophiliacs have been in touch with, during their long-term replacement therapy. Our results seem in keeping with other studies on different type of patients, where a low degree of quasispecies variability has been demonstrated in relationship with the progression and the severity of their liver disease. [source] Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B,,§JOURNAL OF MEDICAL VIROLOGY, Issue 7 2009Fabio Iacomi Abstract A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125,213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L,+,rtL180M,+,rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D,+,sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0,61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5,34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat. J. Med. Virol. 81:1151,1156, 2009. © 2009 Wiley-Liss, Inc. [source] Concordance between semen-derived HIV-1 proviral DNA and viral RNA hypervariable region 3 (V3) envelope sequences in cases where semen populations are distinct from those present in bloodJOURNAL OF MEDICAL VIROLOGY, Issue 1 2002Rebecca Curran Abstract Sequence analysis of the third hypervariable region (V3) of the envelope gene of the HIV-1 was carried out on HIV proviral and viral populations present in blood and semen. Phylogenetically distinct populations of virus were observed in three of the 10 patients analysed. Although the majority of the viruses were predicted to have an R5 phenotype, amino acid differences between blood and semen-derived virus and provirus sequences were observed at sites previously shown to affect cell tropism. Importantly, the semen proviral population was representative of that observed for cell-free virus. This indicates that seminal fluid mononuclear cells are possible sources for the cell-free virus in found in semen. J. Med. Virol. 67:9,19, 2002. © 2002 Wiley-Liss, Inc. [source] Functional studies of an HIV-1 encoded glutathione peroxidaseBIOFACTORS, Issue 1-4 2006Lijun Zhao Abstract In an alternate reading frame overlapping the viral envelope gene, HIV-1 has been shown to encoded a truncated glutathione peroxidase (GPx) module. Essential active site residues of the catalytic core regions of mammalian GPx sequences are conserved in the putative viral GPx (vGPx, encoded by the env-fs gene). Cells transfected with an HIV-1 env-fs construct show up to a 100% increase in GPx enzyme activity, and are protected against the loss of mitochondrial transmembrane potential and subsequent cell death induced by exogenous oxidants or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be more common in HIV-1-infected long-term non-progressors, as compared to HIV-1 isolates from patients developing AIDS. An antioxidant/antiapoptotic protective role of the vGPx is also consistent with the observation that ,1 frameshifting induced by the HIV-1 env-fs sequence AAAAAGA (which contains a potential "hungry" arginine codon, AGA) increases during arginine deficiency, which has been associated with increased oxidative stress. Under arginine-limited conditions, nitric oxide synthase generates superoxide, which rapidly combines with NO to form peroxynitrite, which can cause activated T-cells to undergo apoptosis. Thus, biosynthesis of the HIV-1 GPx as an adaptive response to low arginine conditions might delay oxidant-induced apoptotic cell death, providing an enhanced opportunity for viral replication. [source] Genetic variations associated with psoriasis and psoriatic arthritis found by genome-wide associationDERMATOLOGIC THERAPY, Issue 2 2010Kristina Callis Duffin ABSTRACT Psoriasis and psoriatic arthritis are immune disorders with a complex polygenic basis. HLA-Cw6, which lies in the major histocompatibility region on chromosome 6, is considered the major genetic determinant of psoriasis. Recent genome-wide association studies have identified new variants outside of the MHC with relevance to the immunology of psoriasis. Variants in or near genes that encode subunits of cytokines (IL12B, IL23A) or cytokine receptors (IL23R) are interesting given that the gene product of IL12B, p40, is the target of a recently approved monoclonal antibody therapy for psoriasis (ustekinumab). Association with psoriasis and psoriatic arthritis has been found in TNFAIP3 and TNFIP1, ubiquitin ligases in the NF-,B pathway, and IL13, a Th2 cytokine. Copy number variation of human beta-defensin and late cornified envelope genes also associate with psoriasis. Many of these genetic variations also associate with immune disorders considered psoriatic co-morbidities, including Crohn's disease and diabetes. [source] Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 5 2010Elisa Docampo Objective The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. Methods We tested for association between the LCE3C_LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case,control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C_LCE3B deletion (LCE3C_LCE3B- del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. Results An association of homozygosity for the LCE3C_LCE3B -del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case,control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16,1.81) for association of the LCE3C_LCE3B- del. When the analysis was stratified for serologic data, we observed association in anti,cyclic citrullinated peptide (anti-CCP),positive patients (P = 0.012, OR 1.51 [95% CI 1.09,2.13]) but not in anti-CCP,negative patients. Conclusion We have identified an association between the LCE3C_LCE3B -del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C_LCE3B- del) for autoimmune diseases that is involved in both psoriasis and RA. [source] | |||||||||||||