Evolution of Hypervariable Region 1 of Hepatitis C Virus in Primary Infection

Manzin, Aldo; Solforosi, Laura; Petrelli, Enzo; Macarri, Giampiero; Tosone, Grazia; Piazza, Marcello; Clementi, Massimo

doi:10.1128/jvi.72.7.6271-6276.1998

Cited by 80 publications

(29 citation statements)

References 32 publications

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“…Indeed, epitopes are present in some HVR1 sequences that induce the formation of humoral antibodies, 26,[28][29][30][31] and neutralizing activity has been shown with antibodies directed against particular HVR1 sequences. 7,27,32,33 The observed evolution of HVR1 also could be caused by the activity of HCV-specific CTLs. In chimpanzees that resolved their HCV infection, intrahepatic HCV-specific CTL responses were initially detected at 5 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…HVR1 can encode peptides that generate neutralizing antibodies against HCV, and host immune defenses are probably important factors in driving its evolution. 7,8 In this study of transfusion-transmitted HCV, we analyzed HVR1 in donor-recipient pairs as a function of the time elapsed between the date of transmission and the sample collection date. To determine the time intervals over which this particular genomic region remained unchanged, we studied within-recipient changes in HVR1 in serial specimens.…”

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confidence: 99%

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Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: Divergence over time

et al. 2001

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A total of 240 stored serum specimens from 30 transfusion recipients and 120 blood donors from the TransfusionTransmitted Viruses Study (TTVS) were evaluated with the objective of establishing transmission of hepatitis C virus (HCV) by specific blood donors. Phylogenetic analysis of hypervariable region 1 (HVR1) and HCV genotyping were performed on the genomic region encoding amino acids 329 to 410. Amino acid distances between HVR1 sequences were calculated by the Kimura formula. Bootstrap analysis of HVR1 sequences provided support for linking recipients to specific donors. Linear regression analysis showed no differences between donor and recipient HVR1 sequences 7.9 weeks posttransfusion, but donor and recipient sequences diverged thereafter (r ‫؍‬ 0.690). The initial lag phase in the evolution of HVR1 in the infected recipient was attributed to the time required to mount host immunologic defenses against the virus. Within-recipient divergence in HVR1 was determined from analyses of serial specimens collected within 2 weeks after the alanine transaminase peak, at the end of the original study (1974)(1975)(1976)(1977)(1978)(1979), and in the follow-up study (1987-present). HVR1 remained invariant over a period of 6.7 to 9.5 days (95% CI) during acute infection. Within-patient divergence in HVR1 increased over a period of 11 to 15 years (r ‫؍‬ 0.771), reaching the degree of divergence observed between unlinked subjects. In cases in which transfusion involved more than one HCV subtype, only one of the HCV subtypes established infection in the recipient. Subtype-specific differences in HVR1 were shown. (HEPATOLOGY 2001;34:424-429.)Transmission of RNA viruses from one individual to another may result in selection of one viral quasispecies over another possibly as the result of a different set of host immune pressures. In reports of single source outbreaks, analyses of the envelope genes of human immunodeficiency virus type 1 (HIV-1) or hepatitis C virus (HCV) showed that the viral quasispecies in the recipients usually differed from each other and from that of the source. [1][2][3][4] The inference that the virus established in a given recipient differed from the source virus is not as simple as it appears, for several reasons. The genomic region of the virus that is used to detect differences in viral quasispecies may be critical. Hypervariable region 1 (HVR1) has been used in the study of HCV transmission on the supposition that a very high degree of diversity affords a better chance of distinguishing one viral species from another. 4 In fact, studies on HIV-1 transmission showed that the viral genomic region displaying the highest degree of diversity was less informative for showing transmission than a region that showed a lesser degree of diversity. 5,6 Moreover, the time elapsed between the transmission event and the collection of sample from the recipient may be critical in the application of sequence analysis to the study of virus transmission. HVR1 can encode peptides that generate neutralizing antibodies...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: Divergence over time

et al. 2001

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“…41 Analysis of anti-HVR1 responses in subjects with acute HCV infection revealed that the vigor and cross-reactivity of HVR1 antibody responses were significantly higher in patients with chronic compared with those with acute infection, regardless of their clinical outcome. Because, on primary infection HCV is propagated as a homogeneous population of virions in which a single or a very small number of HVR1 sequences are present, 42 it is likely that cross-reactive immune responses are progressively generated as new HVR1 variants are selected during the course of infection. However, in some of the patients with acute hepatitis cross-reactive, antibodies could be detected early after clinical onset, when only a single molecular species was detectable in the serum, suggesting that cross-reactive anti-HVR1 responses may appear early in the course of HCV infection.…”

Section: Discussionmentioning

confidence: 99%

Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross-reactivity and immune-mediated sequence variation

et al. 1999

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Sequence heterogeneity of hepatitis C virus (HCV) is unevenly distributed along the genome, and maximal variation is confined to a short sequence of the HCV second envelope glycoprotein (E2), designated hypervariable region 1 (HVR1), whose biological function is still undefined. We prospectively studied serological responses to synthetic oligopeptides derived from HVR1 sequences of patients with acute and chronic HCV infection obtained at baseline and after a defined follow-up period. Extensive serological cross-reactivity for unrelated HVR1 peptides was observed in the majority of the patients. Antibody response was restricted to the IgG1 isotype and was focused on the carboxyterminal end of the HVR1 region. Cross-reactive antibodies could be readily elicited following immunization of mice with multiple antigenic peptides carrying HVR1 sequences derived from our patients. The vigor and heterogeneity of cross-reactive antibody responses were significantly higher in patients with chronic hepatitis compared with those with acute hepatitis and in patients infected with HCV type 2 compared with patients infected with other viral genotypes (predominantly type 1), which suggest that higher time-related HVR1 sequence diversification previously described for type 2 may result from immune selection. The finding of a statistically significant correlation between HVR1 sequence variation, and intensity, and crossreactivity of humoral immune responses provided stronger evidence in support of the contention that HCV variant selection is driven by the host's immune pressure. (HEPATOL-OGY 1999;30:537-545.)Hepatitis C virus (HCV) causes chronic infection in more than 60% of exposed individuals through pathogenetic mechanisms that are still poorly understood. 1 Similarly to human immunodeficiency virus (HIV), HCV is able to persist for a virtually indefinite period of time in the host, despite the coexistence of virus-specific immune responses. 2 How HCV induces chronic infection in the face of detectable cellular and humoral immune responses is currently unknown, but the ability of the virus to undergo rapid and substantial sequence modifications is thought to be a major factor in this process. [2][3][4][5][6][7][8][9][10][11] Sequence variation is unevenly distributed along the HCV genome with maximal nucleotide and aminoacid replacements being localized in a stretch of 31 residues at the N-terminus of the second envelope glycoprotein (E2) region named hypervariable region 1 (HVR1). 12 Sequential studies of sequence changes in acute and chronic HCV infection have shown that viral variants are continuously being selected in this region 13,14 and, therefore, HVR1 variation may be a mechanism by which HCV evades neutralizing responses, leading to persistent infection.Most studies point to HVR1 as the major immunogenic domain of E2, although the presence of additional B-cell sites outside HVR1 has been documented, 15 and a conserved B-cell epitope, only partially overlapping with HVR1, has been recently described that competes for ...

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“…49 These types of mutation mostly occur at the outer membrane protein, ie, at the spike protein. 50 These types of mutation increase the sustainability of the HCoVs, by ensuring their escape from both the cell-mediated and humoral immune responses. 51 Despite this, spike proteins have the most potential as a target for vaccine design because of their ability to induce a faster and longer-term mucosal immune response than that of the other proteins 52 and for this reason, has gained much popularity with researchers.…”

Section: B Cell Epitope Identificationmentioning

confidence: 99%

Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach

Oany¹,

Emran²,

Pervin³

2014

DDDT

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Human coronavirus (HCoV), a member of Coronaviridae family, is the causative agent of upper respiratory tract infections and “atypical pneumonia”. Despite severe epidemic outbreaks on several occasions and lack of antiviral drug, not much progress has been made with regard to an epitope-based vaccine designed for HCoV. In this study, a computational approach was adopted to identify a multiepitope vaccine candidate against this virus that could be suitable to trigger a significant immune response. Sequences of the spike proteins were collected from a protein database and analyzed with an in silico tool, to identify the most immunogenic protein. Both T cell immunity and B cell immunity were checked for the peptides to ensure that they had the capacity to induce both humoral and cell-mediated immunity. The peptide sequence from 88–94 amino acids and the sequence KSSTGFVYF were found as the most potential B cell and T cell epitopes, respectively. Furthermore, conservancy analysis was also done using in silico tools and showed a conservancy of 64.29% for all epitopes. The peptide sequence could interact with as many as 16 human leukocyte antigens (HLAs) and showed high cumulative population coverage, ranging from 75.68% to 90.73%. The epitope was further tested for binding against the HLA molecules, using in silico docking techniques, to verify the binding cleft epitope interaction. The allergenicity of the epitopes was also evaluated. This computational study of design of an epitope-based peptide vaccine against HCoVs allows us to determine novel peptide antigen targets in spike proteins on intuitive grounds, albeit the preliminary results thereof require validation by in vitro and in vivo experiments.

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Evolution of Hypervariable Region 1 of Hepatitis C Virus in Primary Infection

Cited by 80 publications

References 32 publications

Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: Divergence over time

Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: Divergence over time

Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross-reactivity and immune-mediated sequence variation

Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach

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