Mixed Infection with Two Types of Hepatitis C Virus Is Probably a Rare Event

Viazov, Sergei; Widell, Anders; Nordenfelt, Erik

doi:10.1007/s150100050005

Cited by 47 publications

(42 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The latter hypothesis is very unlikely given that they display very high divergence rates, and this would imply that these sequences converged toward an existing genotype. In the multiple-infection hypothesis, the competition between two genotypes would necessarily lead to the extinction of the less fit one over time, which is in accordance with the observation that cases of mixed infection in serum are very rare (40,41). Therefore, the use of lymphocytes as hidden reservoirs could be a means for the less fit viruses to maintain their population and persist within an independent reservoir in a chronically infected patient (Fig.…”

Section: Discussionsupporting

confidence: 73%

Specialization of Hepatitis C Virus Envelope Glycoproteins for B Lymphocytes in Chronically Infected Patients

Douam

Bobay

Maurin

et al. 2016

J Virol

View full text Add to dashboard Cite

Hepatitis C virus (HCV) productively infects hepatocytes. Virion surface glycoproteins E1 and E2 play a major role in this restricted cell tropism by mediating virus entry into particular cell types. However, several pieces of evidence have suggested the ability of patientderived HCV particles to infect peripheral blood mononuclear cells. The viral determinants and mechanisms mediating such events remain poorly understood. Here, we aimed at isolating viral determinants of HCV entry into B lymphocytes. For this purpose, we constructed a library of full E1E2 sequences isolated from serum and B lymphocytes of four chronically infected patients. We observed a strong phylogenetic compartmentalization of E1E2 sequences isolated from B lymphocytes in one patient, indicating that E1E2 glycoproteins can represent important mediators of the strong segregation of two specialized populations in some patients. Most of the E1E2 envelope glycoproteins were functional and allowed transduction of hepatocyte cell lines using HCV-derived pseudoparticles. Strikingly, introduction of envelope glycoproteins isolated from B lymphocytes into the HCV JFH-1 replicating virus switched the entry tropism of this nonlymphotropic virus from hepatotropism to lymphotropism. Significant detection of viral RNA and viral proteins within B cells was restricted to infections with JFH-1 harboring E1E2 from lymphocytes and depended on an endocytic, pH-dependent entry pathway. Here, we achieved for the first time the isolation of HCV viral proteins carrying entry-related lymphotropism determinants. The identification of genetic determinants within E1E2 represents a first step for a better understanding of the complex relationship between HCV infection, viral persistence, and extrahepatic disorders. IMPORTANCEHepatitis C virus (HCV) mainly replicates within the liver. However, it has been shown that patient-derived HCV particles can slightly infect lymphocytes in vitro and in vivo, highlighting the existence of lymphotropism determinants within HCV viral proteins. We isolated HCV envelope glycoproteins from patient B lymphocytes that conferred to a nonlymphotropic HCV the ability to enter B cells, thus providing a platform for characterization of HCV entry into lymphocytes. This unusual tropism was accompanied by a loss of entry function into hepatocytes, suggesting that HCV lymphotropic variants likely constitute a distinct but parallel source for viral persistence and immune escape within chronically infected patients. Moreover, the level of genetic divergence of B-cell-derived envelopes correlated with their degree of lymphotropism, underlining a long-term specialization of some viral populations for B-lymphocytes. Consequently, the clearance of both hepatotropic and nonhepatotropic HCV populations may be important for effective treatment of chronically infected patients.

show abstract

Section: Discussionsupporting

confidence: 73%

Specialization of Hepatitis C Virus Envelope Glycoproteins for B Lymphocytes in Chronically Infected Patients

Douam

Bobay

Maurin

et al. 2016

J Virol

View full text Add to dashboard Cite

show abstract

“…In patients with bleeding disorders receiving blood products from donors who have not been screened for anti-HCV antibody and who accordingly are more prone to multiple HCV infection, the prevalence ranges from 0% to 25% (10,16,20,22). The wide variation reported may be explained by the variety of approaches for detecting mixedgenotype infection.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, studies using these approaches to evaluate the prevalence of multitypic HCV infection likely lead to underestimates. Other approaches have been adopted to study multitypic HCV infection specifically (5,9,10,18,(20)(21)(22). Those involving PCR cloning and sequencing are potentially the most effective to identify minority populations, but the impracticality and expense of sequencing large numbers of clones restrict their wider applicability.…”

mentioning

confidence: 99%

Multitypic Hepatitis C Virus Infection Identified by Real-Time Nucleotide Sequencing of Minority Genotypes

Buckton¹,

Ngui²,

Arnold³

et al. 2006

J Clin Microbiol

View full text Add to dashboard Cite

The prevalence of concurrent multitypic hepatitis C virus (HCV) infection is uncertain. A sensitive and specific approach to identifying minority HCV genotypes in blood is presented. Following serum extraction and reverse transcription PCR to amplify cDNA originating from the viral 5 noncoding region, the amplified product mixture was treated with genotype-specific restriction endonuclease to digest the dominant genotype. Residual amplicons were subjected to PCR cloning and then to real-time DNA sequencing using a Pyrosequencer to identify the remaining genotypes. Dilution experiments showed that minority genotypes may be detected when they represent 1:10,000 of the total population and in serum specimens with viral loads as low as 1,000 IU/ml. Of 37 patients with bleeding disorders and 44 injecting drug users, infection by more than one HCV genotype was found in 7 (19%) and 4 (9%) patients, respectively. The low rate of detection in people at high risk of repeated HCV infection suggests that multitypic HCV carriage is uncommon.

show abstract

“…Congruent results from genotyping HCV with different genomic regions have been repeatedly reported in the past and it has commonly been believed that recombination events are selected against or that they generally do not generate viable strains (Prescott et al, 1997; al., 1994;Viazov et al, 2000). However, an infectious HCV chimera comprising the complete open reading frame of a subtype 1b strain and the 59-and 39UTRs of a subtype 1a strain has been constructed and is infectious in vivo (Yagani et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Evidence of intratypic recombination in natural populations of hepatitis C virus

Colina

Casañe

Vásquez³

et al. 2004

Journal of General Virology

114

View full text Add to dashboard Cite

Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of subtypes have been reported. Genotype 1 is the most prevalent genotype found in South America. In the present study, three different genomic regions (59UTR, core and NS5B) of four HCV strains isolated from Peruvian patients were sequenced in order to investigate the congruence of HCV genotyping for these three genomic regions. Phylogenetic analysis using 59UTR-core sequences found strain PE22 to be related to subtype 1b. However, the same analysis using the NS5B region found it to be related to subtype 1a. To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossover event had taken place in the NS5B protein. We discuss the consequences of this observation on HCV genotype classification, laboratory diagnosis and treatment of HCV infection.

show abstract

Mixed Infection with Two Types of Hepatitis C Virus Is Probably a Rare Event

Cited by 47 publications

References 20 publications

Specialization of Hepatitis C Virus Envelope Glycoproteins for B Lymphocytes in Chronically Infected Patients

Specialization of Hepatitis C Virus Envelope Glycoproteins for B Lymphocytes in Chronically Infected Patients

Multitypic Hepatitis C Virus Infection Identified by Real-Time Nucleotide Sequencing of Minority Genotypes

Evidence of intratypic recombination in natural populations of hepatitis C virus

Contact Info

Product

Resources

About