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Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.

Afrasiabi M, Hosseini SY, Yaghobi R, Fattahi MR, Ardebili M, Khodadad M - Jundishapur J Microbiol (2015)

Bottom Line: Then, the obtained sequences were compared with the reference sequences and final phylogenic tree was constructed.Checking different clones of this patient confirmed V36L, as the dominant mutation while R155K was detected only in a few cases.It seems that checking HCV patients before protease inhibitor treatment are necessary in the region.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.

ABSTRACT

Background: Exploring the rate of naturally occurring NS3 protease mutants in HCV infected population is influential in the future therapeutic approaches.

Objectives: This study explored naturally occurring resistant mutations to protease inhibitors in a pilot study.

Patients and methods: We analyzed NS3 gene sequences in 7 HCV infected patients, referred to the central liver center, south of Iran. The protease domain was amplified by PCR followed by product extraction. Amplified NS3 genes were cloned by TA/cloning system. For each patient, clonal-sequencing was performed to improve mutation detection sensitivity. Then, the obtained sequences were compared with the reference sequences and final phylogenic tree was constructed. Afterwards, the sequences were studied to investigate point mutations.

Results: Phylogenetic analysis between reference and amplified sequences demonstrated high similarity of all sequences with genotype 1. Interestingly, crucial protease resistant mutations were detected in V36 and R155 positions in one patient's sequence. Checking different clones of this patient confirmed V36L, as the dominant mutation while R155K was detected only in a few cases.

Conclusions: As revealed, naturally occurring resistant mutations, especially R155K in protease sequence were identified in 1 out of the 7 patients, so the rate of such mutations is estimated to be high. It seems that checking HCV patients before protease inhibitor treatment are necessary in the region.

No MeSH data available.


The Result of Phylogenic TreeThe results tree indicated that all studied samples (marked by circle or square) belonged to HCV genotype 1. It also, indicated that 4 (filed circle) and 3 (filed square) cases were categorized into 1a and 1b genotypes, respectively. The patient with R155 mutation designated as Shr-MNR1, belonged to genotype 1a.
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fig23112: The Result of Phylogenic TreeThe results tree indicated that all studied samples (marked by circle or square) belonged to HCV genotype 1. It also, indicated that 4 (filed circle) and 3 (filed square) cases were categorized into 1a and 1b genotypes, respectively. The patient with R155 mutation designated as Shr-MNR1, belonged to genotype 1a.

Mentions: All sequencing results for each patient were collected and consensus sequences were retrieved after their alignment. These consensus sequences were submitted to NCBI GeneBank with accession numbers of KJ564294 to KJ564300. The constructed phylogenic tree demonstrated that all our sample sequences are placed in the branch of genotype 1a or 1b, as shown in Figure 2. Of 7 analyzed cases, there were four KJ564297-300 and three KJ564294-96 samples with the genotypes 1a and 1b, respectively.


Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran.

Afrasiabi M, Hosseini SY, Yaghobi R, Fattahi MR, Ardebili M, Khodadad M - Jundishapur J Microbiol (2015)

The Result of Phylogenic TreeThe results tree indicated that all studied samples (marked by circle or square) belonged to HCV genotype 1. It also, indicated that 4 (filed circle) and 3 (filed square) cases were categorized into 1a and 1b genotypes, respectively. The patient with R155 mutation designated as Shr-MNR1, belonged to genotype 1a.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644313&req=5

fig23112: The Result of Phylogenic TreeThe results tree indicated that all studied samples (marked by circle or square) belonged to HCV genotype 1. It also, indicated that 4 (filed circle) and 3 (filed square) cases were categorized into 1a and 1b genotypes, respectively. The patient with R155 mutation designated as Shr-MNR1, belonged to genotype 1a.
Mentions: All sequencing results for each patient were collected and consensus sequences were retrieved after their alignment. These consensus sequences were submitted to NCBI GeneBank with accession numbers of KJ564294 to KJ564300. The constructed phylogenic tree demonstrated that all our sample sequences are placed in the branch of genotype 1a or 1b, as shown in Figure 2. Of 7 analyzed cases, there were four KJ564297-300 and three KJ564294-96 samples with the genotypes 1a and 1b, respectively.

Bottom Line: Then, the obtained sequences were compared with the reference sequences and final phylogenic tree was constructed.Checking different clones of this patient confirmed V36L, as the dominant mutation while R155K was detected only in a few cases.It seems that checking HCV patients before protease inhibitor treatment are necessary in the region.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterohepatology Research Center (GEHRC), Shiraz University of Medical Sciences, Shiraz, IR Iran.

ABSTRACT

Background: Exploring the rate of naturally occurring NS3 protease mutants in HCV infected population is influential in the future therapeutic approaches.

Objectives: This study explored naturally occurring resistant mutations to protease inhibitors in a pilot study.

Patients and methods: We analyzed NS3 gene sequences in 7 HCV infected patients, referred to the central liver center, south of Iran. The protease domain was amplified by PCR followed by product extraction. Amplified NS3 genes were cloned by TA/cloning system. For each patient, clonal-sequencing was performed to improve mutation detection sensitivity. Then, the obtained sequences were compared with the reference sequences and final phylogenic tree was constructed. Afterwards, the sequences were studied to investigate point mutations.

Results: Phylogenetic analysis between reference and amplified sequences demonstrated high similarity of all sequences with genotype 1. Interestingly, crucial protease resistant mutations were detected in V36 and R155 positions in one patient's sequence. Checking different clones of this patient confirmed V36L, as the dominant mutation while R155K was detected only in a few cases.

Conclusions: As revealed, naturally occurring resistant mutations, especially R155K in protease sequence were identified in 1 out of the 7 patients, so the rate of such mutations is estimated to be high. It seems that checking HCV patients before protease inhibitor treatment are necessary in the region.

No MeSH data available.