Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

Moreau, Isabelle; Levis, John M.; Crosbie, Órla; Kenny-Walsh, Elizabeth; Fanning, Liam J.

doi:10.1186/1743-422x-5-78

Cited by 21 publications

(20 citation statements)

References 63 publications

(87 reference statements)

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“…On the other hand, VLPs can induce strong immune responses in the absence of adjuvants (Lechmann et al, 2001). Due to their particulate nature, they may efficiently reach the MHC class I pathway in vivo and induce CD8+ T cells or CTL responses (Moron et al, 2003). However, cellular immune responses induced by VLPs in the absence of certain adjuvants may fail to induce immunity against recombinant vaccinia challenge (Storni et al, 2002).…”

Section: Control Of Infection In a Surrogate Challenge Modelmentioning

confidence: 99%

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Recombinant in vitro assembled hepatitis C virus core particles induce strong specific immunity enhanced by formulation with an oil-based adjuvant

Acosta‐Rivero¹,

Poutou²,

Alvarez‐Lajonchere³

et al. 2009

Biol. Res.

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In the present work, immunogenicity of recombinant in vitro assembled hepatitis C virus core particles, HCcAg.120-VLPs, either alone or in combination with different adjuvants was evaluated in BALB/c mice. HCcAg.120-VLPs induced high titers of anti-HCcAg.120 antibodies and virus-specific cellular immune responses. Particularly, HCcAg.120-VLPs induced specific delayed type hypersensitivity, and generated a predominant T helper 1 cytokine profile in immunized mice. In addition, HCcAg.120-VLPs prime splenocytes proliferate in vitro against different HCcAg.120-specific peptides, depending on either the immunization route or the adjuvant used. Remarkably, immunization with HCcAg.120-VLPs/Montanide ISA888 formulation resulted in a significant control of vaccinia virus titer in mice after challenge with a recombinant vaccinia virus expressing HCV core protein, vvCore. Animals immunized with this formulation had a marked increase in the number of IFN-γ producing spleen cells, after stimulation with P815 cells infected with vvCore. These results suggest the use of recombinant HCV core particles as components of therapeutic or preventive vaccine candidates against HCV.

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Section: Control Of Infection In a Surrogate Challenge Modelmentioning

confidence: 99%

“…One of the challenges facing the development of HCV vaccine is their extensive genetic variation (Moreau et al, 2008). HCcAg is among the most conserved proteins in HCV (Bukh et al, 1994) and is known to induce sensitization of both CD4+ and CD8+ lymphocytes (Lechner et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Recombinant in vitro assembled hepatitis C virus core particles induce strong specific immunity enhanced by formulation with an oil-based adjuvant

Acosta‐Rivero¹,

Poutou²,

Alvarez‐Lajonchere³

et al. 2009

Biol. Res.

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“…1). As in other RNA viruses (18,31,32,38,51,52,66), these genetic intrahost variants are thought to serve as the templates on which evolutionary mechanisms, such as recombination, drift, bottlenecking, or positive/negative selective pressures, act to shape variation at the consensus level between hosts (i.e., interhost diversity) (Fig. 1).…”

mentioning

confidence: 99%

“…In addition to consensus sequence, the genetic composition of intrahost viral populations has been shown to be essential for maintaining the fitness of poliovirus populations in vivo (70) and for influencing hepatitis C virus (HCV) and human immunodeficiency virus (HIV) pathogenesis and disease outcome (18,32,38,51,66). For instance, in the case of HCV, high viral diversity was observed in individuals who presented with mild chronic hepatitis rather than severe hepatic injury (66), while low viral diversity posttreatment was…”

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confidence: 99%

Genome-Wide Patterns of Intrahuman Dengue Virus Diversity Reveal Associations with Viral Phylogenetic Clade and Interhost Diversity

Parameswaran

Charlebois

Téllez

et al. 2012

J Virol

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Analogous to observations in RNA viruses such as human immunodeficiency virus, genetic variation associated with intrahost dengue virus (DENV) populations has been postulated to influence viral fitness and disease pathogenesis. Previous attempts to investigate intrahost genetic variation in DENV characterized only a few viral genes or a limited number of full-length genomes. We developed a whole-genome amplification approach coupled with deep sequencing to capture intrahost diversity across the entire coding region of DENV-2. Using this approach, we sequenced DENV-2 genomes from the serum of 22 Nicaraguan individuals with secondary DENV infection and captured ϳ75% of the DENV genome in each sample (range, 40 to 98%). We identified and quantified variants using a highly sensitive and specific method and determined that the extent of diversity was considerably lower than previous estimates. Significant differences in intrahost diversity were detected between genes and also between antigenically distinct domains of the Envelope gene. Interestingly, a strong association was discerned between the extent of intrahost diversity in a few genes and viral clade identity. Additionally, the abundance of viral variants within a host, as well as the impact of viral mutations on amino acid encoding and predicted protein function, determined whether intrahost variants were observed at the interhost level in circulating Nicaraguan DENV-2 populations, strongly suggestive of purifying selection across transmission events. Our data illustrate the value of high-coverage genome-wide analysis of intrahost diversity for high-resolution mapping of the relationship between intrahost diversity and clinical, epidemiological, and virological parameters of viral infection. N early three billion people worldwide are at risk for infection with dengue virus (DENV), a Flavivirus transmitted by the mosquitoes Aedes aegypti and A. albopictus (for reviews, see references 24 and 25). DENV is an RNA virus with a single-stranded, nonsegmented RNA genome ϳ10.7 kb in length, which encodes three structural proteins (capsid [C], premembrane/membrane [prM/M], and envelope ]E]) and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). There are four closely related serotypes of DENV (DENV-1 to DENV-4) that can cause asymptomatic infections or clinical illnesses ranging from the self-limiting but debilitating dengue fever to the lifethreatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are characterized by vascular leakage (76). Even though several factors, such as viral genetics, preexisting heterotypic immunity (i.e., immunity to a different serotype due to a prior infection), the sequence of infection with distinct serotypes, and host genetics appear to influence disease severity (23,35,53,54,58,61,69), the precise causes for progression to severe disease remain unknown.The four DENV serotypes share limited identity, with 25 to 40% variability observed between serotypes at the amino acid level (30, 68)....

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“…Our study aimed to investigate, by describing chronic HCV HVR1 QS evolution over short intervals, whether previously described associations between low QS complexity and high QS diversity could be exploited, in order to optimize the timing of treatment (Fan et al, 2009;Moreau et al, 2008). Additionally, our 2-4 week sample intervals allowed us to provide novel insights into shortinterval HVR1 QS change in chronic infection.…”

Section: Discussionmentioning

confidence: 99%

Intensive temporal mapping of hepatitis C hypervariable region 1 quasispecies provides novel insights into hepatitis C virus evolution in chronic infection

Schmidt-Martin

Crosbie

Kenny-Walsh

et al. 2015

Journal of General Virology

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Hepatitis C virus (HCV) is an RNA virus which exists as swarms of closely related viruses known as quasispecies (QS).A number of studies have demonstrated associations between QS hypervariable region 1 (HVR1) characteristics (diversity and complexity) and treatment success. We investigated HCV QS change in chronic infection over intervals of 2-4 weeks in 23 chronically infected individuals to describe the natural history of virus evolution and establish whether HCV QS characteristics could be used to individualize treatment regimens at a molecular level. HVR1 QS diversity, complexity and divergence continue to change in an unpredictable fashion in chronic infection even where there is little phylogenetic change, which is likely to preclude the use of these features in treatment individualization. Our phylogenetic analysis identified no change in the HVR1 QS in 12 subjects, minor change in four subjects and we describe a time-ordered phylogeny for the first time over a period as short as 16 weeks in seven subjects. We identified the existence of multiple subpopulation infections using partitioned analysis of QS and illustrated how subpopulations were sequentially replaced in a number of subjects. We illustrated marked variation in the nucleotide substitution per codon position between patients with sequence change and those without change in the phylogenetic tree. Analysis of codon-specific selection pressures identified a number of codons under purifying selection, suggesting that these code for structurally conserved amino acids. We also identified sections of the HVR1 under positive selection with marked sequence heterogeneity, suggesting that these may be potential epitope-binding sites.

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Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

Cited by 21 publications

References 63 publications

Recombinant in vitro assembled hepatitis C virus core particles induce strong specific immunity enhanced by formulation with an oil-based adjuvant

Recombinant in vitro assembled hepatitis C virus core particles induce strong specific immunity enhanced by formulation with an oil-based adjuvant

Genome-Wide Patterns of Intrahuman Dengue Virus Diversity Reveal Associations with Viral Phylogenetic Clade and Interhost Diversity

Intensive temporal mapping of hepatitis C hypervariable region 1 quasispecies provides novel insights into hepatitis C virus evolution in chronic infection

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