Evolution of hepatitis C viral quasispecies after liver transplantation

Lyra, André Castro; Fan, Xiaofeng; Lang, Dorothy; Yusim, Karina; Ramrakhiani, Sanjay; Brunt, Elizabeth M.; Korber, Bette T.; Perelson, Alan S.; Bisceglie, Adrian M. Di

doi:10.1053/gast.2002.36546

Cited by 56 publications

(63 citation statements)

References 25 publications

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“…The hypothesis that virus evolution can drive disease progression is supported further by the observation that the population diversity, as well as the ratio of amino acid changing to silent substitutions was higher in individuals with severe liver disease (Cabot et al, 2000;Curran et al, 2002). Similar patterns have been observed in studies of virus evolution following liver transplants in patients with mild and severe disease (Lyra et al, 2002). Investigation of the expected patterns of diversity and rates of evolution in patients with different severity of disease under various assumptions will benefit from further mathematical modelling.…”

Section: Discussionmentioning

confidence: 57%

“…This concept is very difficult to test with data. Studies have quantified sequence diversity and the rate of virus evolution in patients who differ in the severity of liver disease (Cabot et al, 2000;Curran et al, 2002;Farci, 2001;Lyra et al, 2002;Major et al, 1999;Thomson et al, 2001). Even if virus evolution does drive disease progression -as suggested here -this does not mean that one would expect higher virus diversity or faster evolution in patients with severe compared to mild disease.…”

Section: Discussionmentioning

confidence: 93%

“…Therefore, if pathology develops as a result of virus evolution towards antigenic escape, it is possible that patients with severe disease show reduced levels of virus diversification and evolution compared to patients with milder disease. Data on virus diversity have given rise to different and contradictory results (Cabot et al, 2000;Curran et al, 2002;Farci, 2001;Lyra et al, 2002;Major et al, 1999;Thomson et al, 2001). Studies with HCV-infected patients report the emergence of antibody escape mutants early after infection (Farci et al, 2000), while data from the chimpanzee model argue against the frequent occurrence of antibody escape mutants during the early stages of the infection (Major et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses

Wodarz

2003

Journal of General Virology

160

111

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This paper investigates the role of CTL and antibody responses in hepatitis C virus (HCV) dynamics and pathology. Mathematical models suggest that a strong CTL response is required for resolution of HCV infection and that a weak CTL response can result in persistent infection. According to the model, establishment of persistent infection is accompanied mainly by an ongoing antibody response, while CTLs are not maintained at high levels. In the model, this outcome correlates with absence of pathology. Persistent infection in the face of an ongoing antibody response can result in evolution of antigenic escape. According to the model, evolution towards escape from antibodies can shift the balance of immune responses so that the weak CTL levels become increasingly more dominant relative to antibodies. This shift results in onset of liver pathology as the virus evolves towards increased levels of antigenic escape. Therefore, the relative balance of the immune response can be a decisive factor that determines whether patients are asymptomatic or whether pathology is observed. Virus evolution can shift this balance towards pathology over time. Theoretical results are discussed in the context of published data.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses

Wodarz

2003

Journal of General Virology

160

111

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“…20 The transmission and propagation of the major pretransplant sequence was associated with more progressive disease in one study and correlations like with disease outcomes are conflicting. 20,21,45,46 However, we can propose some questions that require answering: Do the following prognosticate different outcomes?…”

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confidence: 99%

Hepatitis C virus quasispecies: Misunderstood and mistreated?

McCaughan

Laskus

Vargas

2003

Liver Transplantation

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“…Our results show that in the context of a new environment and transplant related factors, which include immunosuppression and a new liver, the genetic codes of both CD 81 binding regions are kept relatively stable. Other regions of the HCV genetic code, such as hypervariable region 1 (HVR1), NS2 and NS3 have been reported to undergo considerable variability as soon as a few months after liver transplantation [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

<![CDATA[<B>CD<SUB>81</SUB> binding regions of hepatitis C virus remain conserved after liver transplantation</B>]]>

Lyra¹,

Fan²,

Bisceglie³

2004

Braz J Infect Dis

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CD 81 is a surface-associated protein expressed in the membranes of mammalian cells. It has been suggested that CD 81 interacts with hepatitis C virus E2 protein, and thus might facilitate the entry of HCV into hepatocytes. The envelope-binding site appears to involve amino acids (aa) 480-493 and 544-551 within the E2 glycoprotein. Little is known about the quasispecies genetic diversity of these two regions. We studied four patients who underwent transplantation for HCVrelated cirrhosis and who developed recurrent hepatitis C. We evaluated HCV quasispecies diversity in serum samples obtained at the time of transplantation and at several time points thereafter. Quasispecies diversity was assessed by cloning and sequencing of viral isolates, with computer analysis of evolution models. The genetic distance in the region that spans aa 480 to 493 was 0.019 ± 0.004 before the transplant, and 0.039 ± 0.014 after the transplant (p=0.324). In the aa 544 to 551 region, the pre-transplant genetic distance was 0.012 ± 0.008 and the post-transplant distance, 0.010 ± 0.007 (p=0.890). There was also no significant difference between the number of nonsynonymous substitutions per nonsynonymous site before and after transplantation. In conclusion, the HCV genetic sequences of putative CD 81 binding regions aa 480-493 and aa 544-551 did not diversify significantly after liver transplantation. This may favor HCV re-infection of the allograft after liver transplantation.

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Evolution of hepatitis C viral quasispecies after liver transplantation

Cited by 56 publications

References 25 publications

Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses

Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses

Hepatitis C virus quasispecies: Misunderstood and mistreated?

<![CDATA[<B>CD<SUB>81</SUB> binding regions of hepatitis C virus remain conserved after liver transplantation</B>]]>

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