Limits...
A high variability of mixed infections and recent recombinations of hepatitis B virus in Laos.

Andernach IE, Jutavijittum P, Samountry B, Yousukh A, Thammavong T, Hübschen JM, Muller CP - PLoS ONE (2012)

Bottom Line: Using a published mutation rate of 4.2 × 10(-5) mutations per site and year, the observed minimum genetic distances of 0-0.60% between parent strain and recombinant fragment would correspond to 0-71 years of evolution from a most recent common ancestor (MRCA).Thus several lines of evidence are suggestive of recent independent recombination events, a proportion of these even occurring within the same donors.In conclusion, our analyses revealed a high variability of mixed infections as a very probable breeding ground of multiple variable recombination events in Laos that so far have not led to new dominant strains.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Centre de Recherche Public-Santé/National Public Health Laboratory, Luxembourg, Luxembourg.

ABSTRACT
In Lao PDR, where more than 8% of the population are chronic carriers of HBsAg, multiple genotypes and subgenotypes co-circulate and are prone to generate recombinant viruses. Phylogenetic analyses of multiple clones per donor revealed mixed infections of subgenotypes B1, B2, B4, C1, C5, I1 and I2 in almost 6% of HBsAg positive rejected blood donors. Recombination analyses and distance calculations furthermore showed that about 65% (17/26) of the mixed infected donors showed recombinations in the S-gene alone, involving the predominant genotypes B and C. These results suggest that, at least in Laos, hepatitis B virus (HBV) mixed infections lead to frequent recombinations. In many donors with recombinant strains, the recombinant fragment and a non-recombinant strain of the same genotype co-existed (127/185 analysed recombinant fragments). For a large proportion of these (60/127), the most closely related known virus was found, although not always exclusively, in the same donor. Recombinant virus strains are largely distinct. This is reflected in an unexpected diversity in recombination breakpoints and the relatively rare recombinations with identical recombination patterns of the same genotypes in different donors. Recent recombination events would explain the limited spread of each of the recombinants. Using a published mutation rate of 4.2 × 10(-5) mutations per site and year, the observed minimum genetic distances of 0-0.60% between parent strain and recombinant fragment would correspond to 0-71 years of evolution from a most recent common ancestor (MRCA). Thus several lines of evidence are suggestive of recent independent recombination events, a proportion of these even occurring within the same donors. In conclusion, our analyses revealed a high variability of mixed infections as a very probable breeding ground of multiple variable recombination events in Laos that so far have not led to new dominant strains.

Show MeSH

Related in: MedlinePlus

Phylogenetic clustering of selected HBV/B subgenotype B3, B5, B7 and B8 strains from GenBank and selected genotype B strains from Laos.Non-subgenotypable clones are indicated by red diamonds. Scale bar indicates nucleotide substitutions per site.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3285149&req=5

pone-0030245-g001: Phylogenetic clustering of selected HBV/B subgenotype B3, B5, B7 and B8 strains from GenBank and selected genotype B strains from Laos.Non-subgenotypable clones are indicated by red diamonds. Scale bar indicates nucleotide substitutions per site.

Mentions: In the other 17 donors with mixed-infections at least one clone showed signs of recombinations, and at least one clone showed no such evidence. 16 of these donors had non-recombined clones, that were assigned to genotype C, 15 to genotype B and 1 to genotype I, with subgenotypes C1 (n = 16), C5 (n = 1), B4 (n = 14) and I1 (n = 1) (Table 2). Strains of one donor were attributed to genotype C, but clustered separately from all HBV/C subgenotypes. Additionally, genotype B clones from 3 donors could not be subgenotyped, as the reference strains for genotype B subgenotypes B3, B5, B7 and B8 clustered interspersed with each other and the investigated strains (Figure 1).


A high variability of mixed infections and recent recombinations of hepatitis B virus in Laos.

Andernach IE, Jutavijittum P, Samountry B, Yousukh A, Thammavong T, Hübschen JM, Muller CP - PLoS ONE (2012)

Phylogenetic clustering of selected HBV/B subgenotype B3, B5, B7 and B8 strains from GenBank and selected genotype B strains from Laos.Non-subgenotypable clones are indicated by red diamonds. Scale bar indicates nucleotide substitutions per site.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285149&req=5

pone-0030245-g001: Phylogenetic clustering of selected HBV/B subgenotype B3, B5, B7 and B8 strains from GenBank and selected genotype B strains from Laos.Non-subgenotypable clones are indicated by red diamonds. Scale bar indicates nucleotide substitutions per site.
Mentions: In the other 17 donors with mixed-infections at least one clone showed signs of recombinations, and at least one clone showed no such evidence. 16 of these donors had non-recombined clones, that were assigned to genotype C, 15 to genotype B and 1 to genotype I, with subgenotypes C1 (n = 16), C5 (n = 1), B4 (n = 14) and I1 (n = 1) (Table 2). Strains of one donor were attributed to genotype C, but clustered separately from all HBV/C subgenotypes. Additionally, genotype B clones from 3 donors could not be subgenotyped, as the reference strains for genotype B subgenotypes B3, B5, B7 and B8 clustered interspersed with each other and the investigated strains (Figure 1).

Bottom Line: Using a published mutation rate of 4.2 × 10(-5) mutations per site and year, the observed minimum genetic distances of 0-0.60% between parent strain and recombinant fragment would correspond to 0-71 years of evolution from a most recent common ancestor (MRCA).Thus several lines of evidence are suggestive of recent independent recombination events, a proportion of these even occurring within the same donors.In conclusion, our analyses revealed a high variability of mixed infections as a very probable breeding ground of multiple variable recombination events in Laos that so far have not led to new dominant strains.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Centre de Recherche Public-Santé/National Public Health Laboratory, Luxembourg, Luxembourg.

ABSTRACT
In Lao PDR, where more than 8% of the population are chronic carriers of HBsAg, multiple genotypes and subgenotypes co-circulate and are prone to generate recombinant viruses. Phylogenetic analyses of multiple clones per donor revealed mixed infections of subgenotypes B1, B2, B4, C1, C5, I1 and I2 in almost 6% of HBsAg positive rejected blood donors. Recombination analyses and distance calculations furthermore showed that about 65% (17/26) of the mixed infected donors showed recombinations in the S-gene alone, involving the predominant genotypes B and C. These results suggest that, at least in Laos, hepatitis B virus (HBV) mixed infections lead to frequent recombinations. In many donors with recombinant strains, the recombinant fragment and a non-recombinant strain of the same genotype co-existed (127/185 analysed recombinant fragments). For a large proportion of these (60/127), the most closely related known virus was found, although not always exclusively, in the same donor. Recombinant virus strains are largely distinct. This is reflected in an unexpected diversity in recombination breakpoints and the relatively rare recombinations with identical recombination patterns of the same genotypes in different donors. Recent recombination events would explain the limited spread of each of the recombinants. Using a published mutation rate of 4.2 × 10(-5) mutations per site and year, the observed minimum genetic distances of 0-0.60% between parent strain and recombinant fragment would correspond to 0-71 years of evolution from a most recent common ancestor (MRCA). Thus several lines of evidence are suggestive of recent independent recombination events, a proportion of these even occurring within the same donors. In conclusion, our analyses revealed a high variability of mixed infections as a very probable breeding ground of multiple variable recombination events in Laos that so far have not led to new dominant strains.

Show MeSH
Related in: MedlinePlus