RESUMO
Human immunodeficiency virus subtype 1B (HIV-1B) binds to the CD4 receptor and co-receptor CCR5 or CXCR4 to enter T lymphocytes. The amino acid sequence of the HIV envelope glycoprotein V3 region determines the co-receptor tropism, thereby influencing the infectivity of the virus. Our research group previously found that the amino acid at position 22 of the V3 region may affect the infectivity of the virus, and in this study, we tested this hypothesis. We constructed pseudoviruses by changing the amino acids at position 22 of the V3 region in CCR5-tropic and CXCR4-tropic viruses and tested their infectivity. When the amino acid at V3 position 22 was altered in the CCR5- and CXCR4-tropic viruses, their ability to infect cells decreased to 20.6% and 17.14%, respectively. Therefore, we propose that residue 22 in the V3 region of subtype HIV-1B significantly influences the infectivity of the virus.
Assuntos
Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , HIV-1/patogenicidade , Motivos de Aminoácidos , Linhagem Celular , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/química , HIV-1/genética , Humanos , Ligação Proteica , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Receptores de HIV/genética , Receptores de HIV/metabolismo , VirulênciaRESUMO
Pegylated interferon and ribavirin combination therapy effectively suppresses viral replication in 50 %-60 % of hepatitis C virus (HCV)-infected patients. However, HCV-infected patients often display varied responses to therapy, and strains of subtype lb (the most widespread HCV subtype worldwide) have more-severe clinical manifestations, greater viral loads, and poorer responses to interferon treatment. Therefore, understanding the genomic variability of HCV is crucial to treatment of HCV infection. In this study, we used the appropriate software to analyze the nucleotide, and amino acid sequences of the envelope proteins (E1 and E2) of HCV to investigate the extent of their variability in several HCV subtypes (1a, 1b, 2a, 2b, 3a, 4a, 5a and 6a) and calculated the ratio of nonsynonymous to synonymous substitutions (dN/dS) in these proteins to investigate the immunological pressure acting on them. We also predicted the N-glycosylation sites in E1 and E2 to determine their association with viral neutralization. We found that E1 is more variable, has a higher dN/dS ratio, and has more N-glycosylation sites than E2 in HCV subtype 1b. This indicates that the variability of E1, its dN/dS ratio, and its degree of N-glycosylation might play an important role in the treatment of infection with HCV subtype 1b.
Assuntos
Variação Genética , Hepacivirus/genética , Hepatite C/virologia , Proteínas do Envelope Viral/genética , Genótipo , Glicosilação , Hepacivirus/química , Hepacivirus/classificação , Hepacivirus/metabolismo , Humanos , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismoRESUMO
ABSTRACT: Introduction: Hepatitis C virus (HCV) infection is a major public health issue. HCV genotype identification is clinically important to tailor the dosage and duration of treatment, and recombination in intra-patient populations of HCV may lead to the generation of escape mutants, as previously observed for other RNA viruses. Up to now, there is no study assessing HCV genotypes and subtypes in Heilongjiang Province, China.Methods: To determine genotype and phylogenetic analysis of HCV in Heilongjiang Province is crucial. In this study, we amplified 3 genome regions (5'UTR, E1, and NS5B) of 30 HCV patients in Heilongjiang Province, amplified products were analyzed by bioinformatics.Results: We found that 23 specimens had concordant subtypes in the 3 gene regions (2a and 1b), 7 HCV patients were considered the recombinants, the recombination pattern of the 7 HCV patients in the 5'UTR, E1, and NS5B region as followed: 1b/2a/1b, 2a/2a/1b, 1b/2a/2a, 1b/2a/1b, 1b/2a/1b, 1b/2a/1b, 2a/2a/1b.Conclusions: The findings in the present study showed that a higher recombination rate (23%) than other researches, and the recombination of 2a/1b in the 5'UTR, E1, and NS5B region was only found in the present study up to now.