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  1. Article ; Online: Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

    Tsuchiya, Naho / Pathipvanich, Panita / Wichukchinda, Nuanjun / Rojanawiwat, Archawin / Auwanit, Wattana / Ariyoshi, Koya / Sawanpanyalert, Pathom

    BMC infectious diseases

    2014  Volume 14, Page(s) 565

    Abstract: Background: Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still ... ...

    Abstract Background: Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand.
    Methods: All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models.
    Results: Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification.
    Conclusion: HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia.
    MeSH term(s) Adult ; Aged ; Anti-Retroviral Agents/therapeutic use ; Asia ; CD4 Lymphocyte Count ; Cohort Studies ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; HIV Infections/blood ; HIV Infections/drug therapy ; Humans ; Incidence ; Lamivudine/therapeutic use ; Lipodystrophy ; Male ; Middle Aged ; Nevirapine/therapeutic use ; Stavudine/therapeutic use ; Thailand ; Treatment Failure
    Chemical Substances Anti-Retroviral Agents ; Lamivudine (2T8Q726O95) ; Nevirapine (99DK7FVK1H) ; Stavudine (BO9LE4QFZF)
    Language English
    Publishing date 2014-10-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-2334
    ISSN (online) 1471-2334
    DOI 10.1186/s12879-014-0565-5
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  2. Article: Determination and geographic distribution of Orientia tsutsugamushi serotypes in Thailand by nested polymerase chain reaction.

    Manosroi, Jiradej / Chutipongvivate, Salakchit / Auwanit, Wattana / Manosroi, Aranya

    Diagnostic microbiology and infectious disease

    2006  Volume 55, Issue 3, Page(s) 185–190

    Abstract: Clotted blood samples of 240 scrub typhus patients were collected from 8 Regional Medical Sciences Centers in Thailand during 1999 to 2002. The serotypes of Orientia tsutsugamushi and their geographic distribution were determined. A nested polymerase ... ...

    Abstract Clotted blood samples of 240 scrub typhus patients were collected from 8 Regional Medical Sciences Centers in Thailand during 1999 to 2002. The serotypes of Orientia tsutsugamushi and their geographic distribution were determined. A nested polymerase chain reaction (PCR) was used to identify the serotypes of O. tsutsugamushi. The number of patients with positive results for O. tsutsugamushi was 25.0%. Two serotypes, Karp and Kato, were detected in these samples. No Gilliam serotype was detected from any of the study locations. The PCR products were sequenced using an automated DNA sequencer. The nucleotide sequence of gene encoding 56-kDa protein from these samples showed a high sequence homology with the reference sequence of O. tsutsugamushi Karp and Kato serotypes. O. tsutsugamushi Karp serotype was predominant throughout Thailand with the percentage of 96.8% of the total serotype-positive patients, whereas 3.2% for Kato serotype was observed only in the south. The highest number among the region of Karp serotype-positive patients of 31.6% was found in the northeast.
    MeSH term(s) Adolescent ; Adult ; Child ; Genotype ; Humans ; Middle Aged ; Orientia tsutsugamushi/classification ; Orientia tsutsugamushi/genetics ; Polymerase Chain Reaction/methods ; Scrub Typhus/epidemiology ; Scrub Typhus/microbiology ; Sequence Analysis, DNA ; Serotyping/methods ; Thailand/epidemiology
    Language English
    Publishing date 2006-07
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 604920-5
    ISSN 0732-8893
    ISSN 0732-8893
    DOI 10.1016/j.diagmicrobio.2006.01.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Changing burden of HIV/AIDS to clinical settings in Northern Thailand over 15 years.

    Pathipvanich, Panita / Tsuchiya, Naho / Rojanawiwat, Archawin / Schmidt, Wolf-Peter / Auwanit, Wattana / Sawanpanyalert, Pathom / Ariyoshi, Koya

    Japanese journal of infectious diseases

    2013  Volume 66, Issue 5, Page(s) 375–378

    Abstract: We conducted a hospital-based descriptive study to describe the changing pattern of patient numbers, characteristics, and mortality rates among human immunodeficiency virus (HIV)-infected patients in northern Thailand over 15 years. The survival status ... ...

    Abstract We conducted a hospital-based descriptive study to describe the changing pattern of patient numbers, characteristics, and mortality rates among human immunodeficiency virus (HIV)-infected patients in northern Thailand over 15 years. The survival status on October 31, 2010 of all HIV-infected adults who attended an HIV center in a government hospital between 1995 and 2010 was ascertained. In total, 3,706 patients were registered, 2,118 (57.2%) of which were male. The survival status of 3,439 patients (92.9%) was available. In addition, 1,543 deaths were identified out of 12,858 person-year-observations (PYO) resulting in a mortality rate of 12.4 deaths/100 PYO (95% confidence interval [CI], 11.3-13.0). An initial decline in mortality rates was observed prior to 1999, probably because of an increase in the proportion of less symptomatic patients. After the introduction of the national highly active antiretroviral therapy (HAART) program, a profound decline in mortality rates was observed, reaching 2.0 deaths/100 PYO (95% CI, 1.4-2.9) in 2010. Simultaneously, the number of patients on follow-up increased by nearly fourfold. Although HAART has drastically improved the survival of HIV-infected patients, the number of patients receiving therapy at this HIV clinic has substantially increased. While referral of HIV patients to general physicians' care should be urged, we cannot overemphasize the importance of preventing new HIV infections.
    MeSH term(s) Acquired Immunodeficiency Syndrome/drug therapy ; Acquired Immunodeficiency Syndrome/epidemiology ; Acquired Immunodeficiency Syndrome/mortality ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Retroviral Agents/therapeutic use ; Antiretroviral Therapy, Highly Active/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Survival Analysis ; Thailand/epidemiology ; Young Adult
    Chemical Substances Anti-Retroviral Agents
    Language English
    Publishing date 2013-07-25
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1478383-6
    ISSN 1884-2836 ; 1344-6304
    ISSN (online) 1884-2836
    ISSN 1344-6304
    DOI 10.7883/yoken.66.375
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Early diagnosis of scrub typhus in Thailand from clinical specimens by nested polymerase chain reaction.

    Manosroi, Jiradej / Chutipongvivate, Salakchit / Auwanit, Wattana / Manosroi, Aranya

    The Southeast Asian journal of tropical medicine and public health

    2003  Volume 34, Issue 4, Page(s) 831–838

    Abstract: The early detection of scrub typhus in Thailand by nested polymerase chain reaction (PCR) is presented. The diagnosis of scrub typhus, from clinical samples obtained from hospitals in the northern part of Thailand, by nested PCR was compared to ... ...

    Abstract The early detection of scrub typhus in Thailand by nested polymerase chain reaction (PCR) is presented. The diagnosis of scrub typhus, from clinical samples obtained from hospitals in the northern part of Thailand, by nested PCR was compared to immunofluorescence (IF) and Weil-Felix (WF) tests. The primer pairs used for the nested PCR were designed on the basis of the nucleotide sequence of the gene that encodes the 56-kDa antigen, and RFLP analysis was used for identification. Clotted blood from 80 patients suspected of scrub typhus infection were tested. With the IF test, antibodies for Orientia tsutsugamushi were observed in 38 patients checking IgM and IgG titers. Only 21 patients showed positive seroconversion while 17 patients were negative. For the WF test, only 13 patients gave a positive seroconversion. In the early stage of infection, 19, 13 and 3 patients were detected with a sensitivity of 90.47% (19/21), 61.90% (13/21) and 14.28% (3/21) by the nested PCR, IF and WF test respectively. Two patients who were negative for seroconvesion by IF and WF were positive by nested PCR. Therefore, this suggests that nested PCR is applicable for specific rapid diagnosis at an early stage of scrub typhus in endemic regions.
    MeSH term(s) Adolescent ; Adult ; Agglutination Tests ; Child ; Fluorescent Antibody Technique ; Humans ; Middle Aged ; Orientia tsutsugamushi/isolation & purification ; Polymerase Chain Reaction/methods ; Polymorphism, Restriction Fragment Length ; Scrub Typhus/diagnosis ; Sensitivity and Specificity ; Thailand
    Language English
    Publishing date 2003-12
    Publishing country Thailand
    Document type Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 800646-5
    ISSN 0125-1562 ; 0038-3619
    ISSN 0125-1562 ; 0038-3619
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Short communication: RNA interference directed against Axin1 upregulates human immunodeficiency virus type 1 gene expression by activating the Wnt signaling pathway in HeLa-derived J111 cells.

    Kameoka, Masanori / Kameoka, Yoko / Utachee, Piraporn / Kurosu, Takeshi / Sawanpanyalert, Pathom / Ikuta, Kazuyoshi / Auwanit, Wattana

    AIDS research and human retroviruses

    2009  Volume 25, Issue 10, Page(s) 1005–1011

    Abstract: Axin1, a regulator of Wnt signaling, was previously identified as playing a negative role in the late phase of human immunodeficiency virus type 1 (HIV-1) replication in HeLa-derived J111 cells. In this report, we studied the molecular mechanism of how ... ...

    Abstract Axin1, a regulator of Wnt signaling, was previously identified as playing a negative role in the late phase of human immunodeficiency virus type 1 (HIV-1) replication in HeLa-derived J111 cells. In this report, we studied the molecular mechanism of how Axin1 regulates HIV-1 replication. HIV-1 transactivator, Tat-dependent viral reporter gene expression was enhanced in J111 cells transfected with small interfering RNA (siRNA) against Axin1. In addition, viral transcription was upregulated in J111 cells transfected with siRNA against Axin1. In contrast, HIV-1 gene expression was not enhanced by transfecting HeLa cells with siRNA against Axin1. The expression levels of T cell factor-4 (TCF4) and beta-catenin were higher in J111 than HeLa cells. In addition, siRNAs against TCF4 and beta-catenin inhibited the Axin1 siRNA-dependent enhancement of HIV-1 gene expression in J111 cells. These results suggest that Axin1 plays a negative role in HIV-1 transcription through the Wnt signaling pathway in J111 cells under normal cell culture conditions.
    MeSH term(s) Axin Protein ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/biosynthesis ; Gene Expression Regulation, Viral ; HIV-1/immunology ; HeLa Cells ; Humans ; RNA Interference ; Repressor Proteins/antagonists & inhibitors ; Signal Transduction ; Transcription Factor 4 ; Transcription Factors/biosynthesis ; Transcription, Genetic ; Up-Regulation ; beta Catenin/biosynthesis ; tat Gene Products, Human Immunodeficiency Virus/biosynthesis
    Chemical Substances AXIN1 protein, human ; Axin Protein ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Repressor Proteins ; TCF4 protein, human ; Transcription Factor 4 ; Transcription Factors ; beta Catenin ; tat Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2009-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/aid.2008.0284
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  6. Article ; Online: Detection of drug resistance-associated and background mutations in human immunodeficiency virus type 1 CRF01_AE protease and reverse transcriptase derived from drug treatment-naive patients residing in central Thailand.

    Auwanit, Wattana / Isarangkura-Na-Ayuthaya, Panasda / Kasornpikul, Dao / Ikuta, Kazuyoshi / Sawanpanyalert, Pathom / Kameoka, Masanori

    AIDS research and human retroviruses

    2009  Volume 25, Issue 6, Page(s) 625–631

    Abstract: CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia, including Thailand. We performed genotypic studies on HIV-1 CRF01_AE protease (PR) and reverse transcriptase (RT) derived from plasma samples from ... ...

    Abstract CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia, including Thailand. We performed genotypic studies on HIV-1 CRF01_AE protease (PR) and reverse transcriptase (RT) derived from plasma samples from drug treatment-naive patients residing in central Thailand. Direct sequencing of amplified CRF01_AE PR and RT genes revealed that drug resistance-associated as well as background mutations were frequently detected in CRF01_AE PR. In contrast, although several background mutations were detected, no drug resistance-associated mutations were observed in CRF01_AE RT. Antiretroviral drugs, including PR inhibitors, have been increasingly used in Thailand. To achieve effective antiretroviral therapy, we propose that it is important to reveal the prevalence of drug resistance-associated mutations among drug treatment-naive patients by further surveillance studies.
    MeSH term(s) Drug Resistance, Viral ; HIV Infections/virology ; HIV Protease/genetics ; HIV Reverse Transcriptase/genetics ; HIV-1/genetics ; HIV-1/isolation & purification ; Humans ; Molecular Sequence Data ; Mutation, Missense ; Sequence Analysis, DNA ; Thailand
    Chemical Substances reverse transcriptase, Human immunodeficiency virus 1 (EC 2.7.7.-) ; HIV Reverse Transcriptase (EC 2.7.7.49) ; HIV Protease (EC 3.4.23.-) ; p16 protease, Human immunodeficiency virus 1 (EC 3.4.23.-)
    Language English
    Publishing date 2009-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/aid.2008.0298
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  7. Article: Substantially exposed but HIV-negative individuals are accumulated in HIV-serology-discordant couples diagnosed in a referral hospital in Thailand.

    Rojanawiwat, Archawin / Ariyoshi, Koya / Pathipvanich, Panita / Tsuchiya, Naho / Auwanit, Wattana / Sawanpanylaert, Pathom

    Japanese journal of infectious diseases

    2009  Volume 62, Issue 1, Page(s) 32–36

    Abstract: The objectives of this study is to characterize HIV-serology-discordant couples diagnosed at a referral hospital in Thailand and to identify risk factors for HIV transmission among married couples. Firstly, cross-sectional analysis was conducted from ... ...

    Abstract The objectives of this study is to characterize HIV-serology-discordant couples diagnosed at a referral hospital in Thailand and to identify risk factors for HIV transmission among married couples. Firstly, cross-sectional analysis was conducted from July 2000 to October 2002. Out of 216 HIV-positive married men who knew the HIV status of their wives, the median number of sexual contacts in 63 men with HIV-negative wives was 6 times per month before the disclosure of HIV status, which did not differ from 153 men with HIV-positive wives. The majority of men with HIV-negative wives never used condoms. The median duration of marriage was 7 years for both groups. Unlike in previous reports, men with HIV-negative wives were significantly more symptomatic (P<0.01), and their CD4+ counts and viral loads did not differ from men with HIV-positive wives. Secondarily, 71 initially discordant couples were longitudinally followed until March 2005. Four were seroconverted out of 132.24 person-years of observation. In multivariate analysis incorporating sex, age, CD4+ count and sexual contact without a condom, shorter duration of marriage (<2 years) was found to be the only risk factor significantly associated with HIV transmission (hazard ratio of 15.2, P=0.04). Individuals substantially exposed to HIV but remaining HIV-negative are accumulated in discordant couples identified in a hospital, except in recently married couples.
    MeSH term(s) AIDS Serodiagnosis ; Adult ; Cross-Sectional Studies ; Family Characteristics ; Female ; HIV Infections/epidemiology ; HIV Infections/transmission ; HIV Seropositivity/epidemiology ; HIV Seropositivity/transmission ; HIV-1 ; Humans ; Male ; Multivariate Analysis ; Proportional Hazards Models ; Referral and Consultation ; Risk Factors ; Sexual Behavior ; Sexual Partners ; Spouses/statistics & numerical data ; Survival Analysis ; Thailand/epidemiology
    Language English
    Publishing date 2009-01
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1478383-6
    ISSN 1884-2836 ; 1344-6304
    ISSN (online) 1884-2836
    ISSN 1344-6304
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  8. Article: Impact of the National Access to Antiretroviral Program on the incidence of opportunistic infections in Thailand.

    Rojanawiwat, Archawin / Tsuchiya, Naho / Pathipvanich, Panita / Pumpradit, Wadchara / Schmidt, Wolf-Peter / Honda, Sumihisa / Auwanit, Wattana / Sawanpanyalert, Pathom / Ariyoshi, Koya

    International health

    2011  Volume 3, Issue 2, Page(s) 101–107

    Abstract: The National Access to Antiretroviral Program caused a decline in HIV mortality in Thailand, but its impact on opportunistic infections (OI) remains unknown. The aim of this study was to compare the incidence of different OIs before and after the ... ...

    Abstract The National Access to Antiretroviral Program caused a decline in HIV mortality in Thailand, but its impact on opportunistic infections (OI) remains unknown. The aim of this study was to compare the incidence of different OIs before and after the initiation of highly active antiretroviral therapy (HAART). Data from a prospective cohort at a hospital in northern Thailand were analysed. In total, 704 patients enrolled from July 2000 to October 2002 and not on HAART were followed up until October 2004. In addition, 409 patients who started HAART between April 2002 and January 2004 were followed up for 24 months. The impact of HAART on OIs was analysed using Cox proportional hazard models. HAART was associated with a strong reduction in OIs. The reduction appeared to vary by type: tuberculosis (TB), adjusted hazard ratio (AHR) = 0.2 (95% CI 0.1-0.5); pneumocystis pneumonia (PCP), AHR = 0.03 (95% CI 0.007-0.1); cryptococcal meningitis, AHR = 0.2 (95% CI 0.1-0.5); and penicilliosis, AHR = 0.1 (95% CI 0.06-0.3). In conclusion, HAART was very effective in reducing OIs, especially PCP. TB and cryptococcal meningitis remained frequent in the early phase of antiretroviral drug therapy. More attention to prophylaxis as well as earlier diagnosis and starting treatment for these OIs is recommended.
    Language English
    Publishing date 2011-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2526175-7
    ISSN 1876-3405 ; 1876-3413
    ISSN (online) 1876-3405
    ISSN 1876-3413
    DOI 10.1016/j.inhe.2010.12.004
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  9. Article ; Online: Appearance of Drug Resistance-Associated Mutations in Human Immunodeficiency Virus Type 1 CRF01_AE Integrase Derived from Drug-Naive Thai Patients.

    Isarangkura-Na-Ayuthaya, Panasda / Kaewnoo, Wiyada / Auwanit, Wattana / de Silva, U Chandimal / Ikuta, Kazuyoshi / Sawanpanyalert, Pathom / Kameoka, Masanori

    AIDS research and human retroviruses

    2010  Volume 26, Issue 12, Page(s) 1341–1343

    Abstract: CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia, including Thailand. We performed genotypic studies on HIV-1 CRF01_AE integrase derived from plasma samples from drug-naive Thai patients. Direct ... ...

    Abstract CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia, including Thailand. We performed genotypic studies on HIV-1 CRF01_AE integrase derived from plasma samples from drug-naive Thai patients. Direct sequencing of amplified CRF01_AE integrase genes revealed that although no primary mutations associated with drug resistance to integrase inhibitors were detected, at least one secondary mutation was found in 96% of samples. Our results indicate that the impact of these mutations on the baseline drug susceptibility of CRF01_AE viruses to integrase inhibitors may need to be addressed prior to the introduction of these drugs in Southeast Asian countries, including Thailand.
    MeSH term(s) Anti-HIV Agents/pharmacology ; Drug Resistance, Viral ; HIV Infections/virology ; HIV Integrase/genetics ; HIV-1/drug effects ; HIV-1/genetics ; HIV-1/isolation & purification ; Humans ; Molecular Sequence Data ; Mutation, Missense ; Plasma/virology ; RNA, Viral/genetics ; Sequence Analysis, DNA ; Thailand
    Chemical Substances Anti-HIV Agents ; RNA, Viral ; p31 integrase protein, Human immunodeficiency virus 1 ; HIV Integrase (EC 2.7.7.-)
    Language English
    Publishing date 2010-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/aid.2010.0140
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  10. Article ; Online: Two N-linked glycosylation sites in the V2 and C2 regions of human immunodeficiency virus type 1 CRF01_AE envelope glycoprotein gp120 regulate viral neutralization susceptibility to the human monoclonal antibody specific for the CD4 binding domain.

    Utachee, Piraporn / Nakamura, Shota / Isarangkura-Na-Ayuthaya, Panasda / Tokunaga, Kenzo / Sawanpanyalert, Pathom / Ikuta, Kazuyoshi / Auwanit, Wattana / Kameoka, Masanori

    Journal of virology

    2010  Volume 84, Issue 9, Page(s) 4311–4320

    Abstract: A recombinant human monoclonal antibody, IgG1 b12 (b12), recognizes a conformational epitope on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) gp120 that overlaps the CD4 binding domain. Although b12 is able to broadly neutralize ...

    Abstract A recombinant human monoclonal antibody, IgG1 b12 (b12), recognizes a conformational epitope on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) gp120 that overlaps the CD4 binding domain. Although b12 is able to broadly neutralize HIV-1 subtype B, C, and D viruses, many HIV-1 CRF01_AE viruses are resistant to b12-mediated neutralization. In this report, we examined the molecular mechanisms underlying the low neutralization susceptibility of CRF01_AE viruses to b12, using recently established CRF01_AE Env recombinant viruses. Our results showed that two potential N-linked glycosylation (PNLG) sites in the V2 and C2 regions of Env gp120 played an important role in regulating the susceptibility of CRF01_AE Env to b12. The locations of these PNLG sites correspond to amino acid positions 186 and 197 in HXB2 Env gp120; thus, they are designated N186 and N197 in this study. Removal of N186 significantly conferred the b12 susceptibility of 2 resistant CRF01_AE Env clones, 65CC4 and 107CC2, while the introduction of N186 reduced the b12 susceptibility of a susceptible CRF01_AE Env clone, 65CC1. In addition, removal of both N186 and N197 conferred the b12 susceptibility of 3 resistant CRF01_AE Env clones, 45PB1, 62PL1, and 101PL1, whereas the removal of either N186 or N197 was not sufficient to confer the b12 susceptibility of these CRF01_AE Env clones. Finally, removal of N197 conferred the b12 susceptibility of 2 resistant CRF01_AE Env clones lacking N186, 55PL1 and 102CC2. Taken together, we propose that two PNLG sites, N186 and N197, in Env gp120 are important determinants of the b12 resistance of CRF01_AE viruses.
    MeSH term(s) Amino Acid Sequence ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/immunology ; Binding Sites ; Epitopes/metabolism ; Glycosylation ; HIV Antibodies/immunology ; HIV Envelope Protein gp120/immunology ; HIV Envelope Protein gp120/metabolism ; HIV-1/immunology ; Humans ; Immunoglobulin G/immunology ; Molecular Sequence Data ; Mutant Proteins/immunology ; Neutralization Tests ; Protein Processing, Post-Translational
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Epitopes ; HIV Antibodies ; HIV Envelope Protein gp120 ; Immunoglobulin G ; Mutant Proteins ; gp120 protein, Human immunodeficiency virus 1
    Language English
    Publishing date 2010-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.02619-09
    Database MEDical Literature Analysis and Retrieval System OnLINE

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