Analysis of hepatitis C viral quasispecies in liver transplantation

García, Javier Moreno; Campo, Santos del; García, Gómez; González, Miguel; Lopez, E; Vázquez-Garza, Javier Nuño; Abete, J. Fortún; Martin, Paul; Marugán, Rafael Bárcena

doi:10.1016/s0041-1345(03)00632-8

Cited by 7 publications

(4 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reinfection occurs within a few hours of graft reperfusion despite the presence of anti-HCV antibodies (Brown, 2005). Evolution of viral quasispecies rapidly changes after transplantation, and only a small fraction of viral variants present before transplantation is selected after LT (Moreno Garcia et al, 2003; Feliu et al, 2004; Brown, 2005; Schvoerer et al, 2007). These observations suggest that HCV has developed efficient strategies to evade host immunity and adapt rapidly to the new host environment.…”

mentioning

confidence: 99%

Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

Fafi‐Kremer

Fofana

Soulier

et al. 2010

Journal of Experimental Medicine

123

162

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

Fafi‐Kremer

Fofana

Soulier

et al. 2010

Journal of Experimental Medicine

123

162

View full text Add to dashboard Cite

show abstract

“…The structural E1 and E2 genes evolve fastest (13) and have the strongest phylogenetic signal (40) as a result of encoding proteins that are recognized by the host immune system. Several studies report that some or most of the pretransplant diversity in the E1E2 region is lost during a viral bottleneck that follows transplantation, possibly reflecting the outgrowth of fitter variants (2,8,9,16,32,41,42). In contrast, some evidence suggests that posttransplant viral dynamics are more complex than a simple population bottleneck; for example, the dominant variant at 7 days posttransplant does not persist in later samples in all cases (2, 42), and the minor variant pretransplant can become dominant (14).…”

mentioning

confidence: 99%

“…In contrast, some evidence suggests that posttransplant viral dynamics are more complex than a simple population bottleneck; for example, the dominant variant at 7 days posttransplant does not persist in later samples in all cases (2,42), and the minor variant pretransplant can become dominant (14). An observed bottleneck could be explained by a founder effect of colonization of the new liver, or result from methodological limitations such as consensus sequencing (28) or single-strand conformation polymorphisms (2,32) and the use of summary statistics (9,32,37,41), which fail to elucidate evolutionary relationships or structure (39,44); grouping results from multiple patients rendering data interpretation difficult (9,27,32,41,42); and temporally restric-tive sampling schemes that limit investigation of long-term evolutionary trends (8,9,16,37).…”

mentioning

confidence: 99%

Unexpected Maintenance of Hepatitis C Viral Diversity following Liver Transplantation

Gray

Strickland

Véras

et al. 2012

J Virol

View full text Add to dashboard Cite

h Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis in up to 20% of individuals, often requiring liver transplantation. Although the new liver is known to be rapidly reinfected, the dynamics and source of the reinfecting virus(es) are unclear, resulting in some confusion concerning the relationship between clinical outcome and viral characteristics. To clarify the dynamics of liver reinfection, longitudinal serum viral samples from 10 transplant patients were studied. Part of the E1/E2 region was sequenced, and advanced phylogenetic analysis methods were used in a multiparameter analysis to determine the history and ancestry of reinfecting lineages. Our results demonstrated the complexity of HCV evolutionary dynamics after liver transplantation, in which a large diverse population of viruses is transmitted and maintained for months to years. As many as 30 independent lineages in a single patient were found to reinfect the new liver. Several later posttransplant lineages were more closely related to older pretransplant viruses than to viruses detected immediately after transplantation. Although our data are consistent with a number of interpretations, the persistence of high viral genetic variation over long periods of time requires an active mechanism. We discuss possible scenarios, including frequency-dependent selection or variation in selective pressure among viral subpopulations, i.e., the population structure. The latter hypothesis, if correct, could have relevance to the success of newer direct-acting antiviral therapies.T he hepatitis C virus (HCV; family Flaviviridae, genus Hepacivirus) infects more than 180 million people worldwide and is a leading global cause of liver disease and cancer (3, 26). Since individuals can remain asymptomatic for decades, the true prevalence is potentially much greater than current estimates of ϳ3% of the world population (50). At present, no vaccine is available, and pharmacological treatment is only moderately successful, particularly for the most prevalent subtypes circulating in the United States and Europe (3), due in part to a prolonged asymptomatic phase of chronic infection that hinders early identification of HCV transmission among individuals. Although the use of direct-acting antiviral drugs (including two recently licensed protease inhibitors) offer improved sustained antiviral response rates (29), drug treatments will not be successful in all patients (47), and antiviral resistance is likely to play a significant role in treatment failure (21). Thus, chronic HCV infection remains a major public health concern.Liver cirrhosis develops in up to 20% of HCV-infected individuals, who will eventually require a liver transplant (3). However, the new liver is infected within minutes following transplant (16), serum viral load increases 10-to 20-fold relative to pretransplant levels (12), and the clinical course of disease is accelerated (11). Characteristics of the infecting virus and its anatomical source(s) are unknown, reflecting the lack of a pr...

show abstract

“…Such a decrease in quasispecies diversity after OLT had previously been observed; it is thought that OLT presents a genetic bottleneck through which only a limited number of selected variants can pass, with many others being eliminated 9‐11. However, the mechanisms determining which variants are selected have never been addressed experimentally.…”

Section: Commentmentioning

confidence: 93%

Survival of the fittest: Selection of hepatitis C virus variants during liver graft reinfection

Mederacke

Hahn

2011

Hepatology

View full text Add to dashboard Cite

End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft. CommentRecurrent hepatitis C after orthotopic liver transplantation (OLT) for hepatitis C-associated end-stage liver disease or hepatocellular carcinoma is a vexing clinical problem. Rapid reinfection of the liver graft by hepatitis C virus (HCV) particles in the blood is nearly universal, and the ensuing disease often runs an accelerated course quickly progressing to graft cirrhosis and retransplantation or death.1 In contrast to hepatitis B, no passive immunoprophylaxis is currently available. The first potent, directly acting antiviral drugs are expected to be licensed only in 2011, and they have not been evaluated in individuals with end-stage liver disease or in the peritransplant setting. The difficulties in creating efficient immunoprophylaxis are in large part due to the high genetic variability of HCV: this relatively small enveloped virus with an approximately 10-kb nonsegmented, plus-strand RNA genome has a highly error-prone RNA-dependent RNA polymerase.2 As a result, HCV exists in the infected host not as a homogeneous population but rather as a large number of variants that are collectively called the quasispecies swarm.3 Therefore, HCV can rapidly respond to selective pressures to which it is subjected by antiviral drugs or cellular and humoral immune responses; this is conceivably a prerequisite for establishing and maintaining a chronic infection. 4 For HCV to infect target cells, the viral envelope glycoproteins, E1 and E2, must interact with at least four (co)receptors on the hepatocyte surface: scavenger receptor BI, the tetraspanin CD81, and two components of the hepatic tight junction (claudin 1 and occludin).5 It has been shown that the humoral immune response is a major driver of HCV E1E2 evolution during chronic infection because antibodies capable of neutralizing most viral variants in the swarm are continuously generated, but neutralization-resistant minor variants pres...

show abstract

Analysis of hepatitis C viral quasispecies in liver transplantation

Cited by 7 publications

References 12 publications

Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

Unexpected Maintenance of Hepatitis C Viral Diversity following Liver Transplantation

Survival of the fittest: Selection of hepatitis C virus variants during liver graft reinfection

Contact Info

Product

Resources

About