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Sustained appearance of drug resistance-associated mutations in HIV-1 CRF01_AE protease and reverse transcriptase derived from protease inhibitor-naive Thai patients. 2010

Duangrat Jullaksorn, and Samatchaya Boonchawalit, and Jiraporn Uttiyoung, and Bongkot Soonthornsata, and Amara Yowang, and Nongkran Krathong, and Sununta Chautrakul, and Kazuyoshi Ikuta, and Amornsak Roobsoong, and Sangkom Kanitvittaya, and Pathom Sawanpanyalert, and Masanori Kameoka
National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Japan.

Previous studies revealed that HIV-1 CRF01_AE viruses derived from antiretroviral drug-naïve Thai patients contained several protease (PR) inhibitor (PI) resistance-associated mutations. In this report, we examined the sustained appearance of drug resistance-associated mutations in CRF01_AE PR and reverse transcriptase (RT). Peripheral blood samples were collected every 3 months from April 2008 to April 2009 from 39 HIV-1-infected Thai patients, including 17 drug-naive and 22 RT inhibitors (RTIs)-treated individuals, and polymerase chain reaction-mediated-amplification and sequencing analysis of the viral genome encoding PR and RT were performed. We successfully analyzed the deduced amino acid sequence of CRF01_AE PR and RT derived from samples continuously collected from 15 drug-naïve and 20 RTIs-treated patients. Drug resistance-associated mutations were continuously detected in CRF01_AE PR derived from most patients. The continuous appearance of such PR mutations was observed not only in the proviral DNA genome derived from peripheral blood mononuclear cells, but also in the viral RNA genome of plasma virus. In contrast, RTI resistance-associated mutations were only sporadically detected in samples derived from drug-naive and RTIs-treated patients, except for the continuous appearance of two mutations in samples derived from two drug-naive patients. Our results demonstrate that many PI resistance-associated mutations and only a few RTI resistance-associated mutations continuously appear in CRF01_AE viruses derived from PI-naïve patients residing in northern Thailand.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013785 Thailand Formerly known as Siam, this is a Southeast Asian nation at the center of the Indochina peninsula. Bangkok is the capital city. Kingdom of Thailand,Siam
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D016333 HIV Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Proteinase,HTLV-III Protease,p16 pol gene product, HIV,p16 protease, HIV,HIV p16 protease,HTLV III Protease,Protease, HIV,Protease, HTLV-III
D017422 Sequence Analysis, DNA A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis. DNA Sequence Analysis,Sequence Determination, DNA,Analysis, DNA Sequence,DNA Sequence Determination,DNA Sequence Determinations,DNA Sequencing,Determination, DNA Sequence,Determinations, DNA Sequence,Sequence Determinations, DNA,Analyses, DNA Sequence,DNA Sequence Analyses,Sequence Analyses, DNA,Sequencing, DNA
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse

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