Temporal Variations in the Hepatitis C Virus Intra-Host Population during Chronic Infection

[Guest guest]

J Virol. 2011 Apr 27. [Epub ahead of print]

Temporal Variations in the Hepatitis C Virus Intra-Host Population during

Chronic Infection.

Ramachandran S, Campo DS, Dimitrova ZE, Xia GL, Purdy MA, Khudyakov YE.

Source

Molecular Epidemiology & Bioinformatics Laboratory, Division of Viral Hepatitis,

Centers for Disease Control and Prevention. 1600 Clifton, Rd, Atlanta, GA 30333.

Abstract

The hepatitis C virus (HCV) intra-host evolution holds keys to understanding

mechanisms responsible for establishment of chronic infections and development

of a vaccine and therapeutics. In this study, intra-host variants of two

variable HCV genomic regions, HVR1 and NS5A, were sequenced from four

treatment-naïve chronically infected patients who were followed up from the

acute stage for 9-18 years. Median joining network analysis indicated that

majority of the HCV intra-host variants were observed only at certain

time-points, but some variants were detectable at more than one time-point. In

all patients, these variants were found organized into communities or

subpopulations. We hypothesize that HCV intra-host evolution is defined by 2

processes: incremental changes within communities through random mutation, and

alternations between coexisting communities. The HCV population was observed to

incrementally evolve within a single community during the first ∼3 years of

infection followed by dispersion into several subpopulations. Two patients

demonstrated this pattern of dispersion for the rest of the observation period,

while HCV variants in the other two patients converged into another single

subpopulation after ∼9-12 years of dispersion. The final subpopulation in

these two patients was under purifying selection. Intra-host HCV evolution in

all four patients was characterized by a consistent increase in negative

selection over time, suggesting the increasing HCV adaptation to the host late

in infection. The data suggest specific staging of the intra-host HCV evolution.

PMID: 21525348 [PubMed - as supplied by publisher]

[Guest guest]

J Virol. 2011 Apr 27. [Epub ahead of print]

Temporal Variations in the Hepatitis C Virus Intra-Host Population during

Chronic Infection.

Ramachandran S, Campo DS, Dimitrova ZE, Xia GL, Purdy MA, Khudyakov YE.

Source

Molecular Epidemiology & Bioinformatics Laboratory, Division of Viral Hepatitis,

Centers for Disease Control and Prevention. 1600 Clifton, Rd, Atlanta, GA 30333.

Abstract

The hepatitis C virus (HCV) intra-host evolution holds keys to understanding

mechanisms responsible for establishment of chronic infections and development

of a vaccine and therapeutics. In this study, intra-host variants of two

variable HCV genomic regions, HVR1 and NS5A, were sequenced from four

treatment-naïve chronically infected patients who were followed up from the

acute stage for 9-18 years. Median joining network analysis indicated that

majority of the HCV intra-host variants were observed only at certain

time-points, but some variants were detectable at more than one time-point. In

all patients, these variants were found organized into communities or

subpopulations. We hypothesize that HCV intra-host evolution is defined by 2

processes: incremental changes within communities through random mutation, and

alternations between coexisting communities. The HCV population was observed to

incrementally evolve within a single community during the first ∼3 years of

infection followed by dispersion into several subpopulations. Two patients

demonstrated this pattern of dispersion for the rest of the observation period,

while HCV variants in the other two patients converged into another single

subpopulation after ∼9-12 years of dispersion. The final subpopulation in

these two patients was under purifying selection. Intra-host HCV evolution in

all four patients was characterized by a consistent increase in negative

selection over time, suggesting the increasing HCV adaptation to the host late

in infection. The data suggest specific staging of the intra-host HCV evolution.

PMID: 21525348 [PubMed - as supplied by publisher]