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  1. Article ; Online: Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients.

    Levin, Myron J / Bacon, Teresa H / Leary, Jeffry J

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2004  Volume 39 Suppl 5, Page(s) S248–57

    Abstract: Antiviral treatment of herpes simplex virus (HSV) infections with nucleoside analogues has been well established for >2 decades, but isolation of drug-resistant HSV from immunocompetent patients has remained infrequent (0.1%-0.7% of isolates) during this ...

    Abstract Antiviral treatment of herpes simplex virus (HSV) infections with nucleoside analogues has been well established for >2 decades, but isolation of drug-resistant HSV from immunocompetent patients has remained infrequent (0.1%-0.7% of isolates) during this period. Even when drug-resistant HSV is isolated from an immunocompetent patient, this virus, with rare exceptions, is cleared normally without adverse clinical outcome. Although drug-resistant HSV is more commonly isolated from immunocompromised patients (4%-7% of isolates) and is more likely to be clinically significant, the prevalence of drug-resistant HSV even among these patients, has been stable over the past 2 decades. Despite this stable prevalence, disease due to drug-resistant HSV remains an important problem for many immunocompromised patients, including those with HIV infection. This article reviews the prevalence, pathogenesis, and implications of drug-resistant HSV infections in HIV-infected patients.
    MeSH term(s) Acyclovir/pharmacology ; Acyclovir/therapeutic use ; Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Drug Resistance, Viral/genetics ; Drug Resistance, Viral/immunology ; HIV Infections/complications ; HIV Infections/immunology ; Herpes Simplex/complications ; Herpes Simplex/drug therapy ; Herpes Simplex/immunology ; Humans ; Immunity, Cellular ; Immunocompetence ; Immunocompromised Host ; Nucleosides/pharmacology ; Nucleosides/therapeutic use ; Recurrence ; Simplexvirus/drug effects ; Simplexvirus/genetics ; Simplexvirus/pathogenicity
    Chemical Substances Antiviral Agents ; Nucleosides ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2004-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1086/422364
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Impact of social support on cognitive symptom burden in HIV/AIDS.

    Atkins, Jana H / Rubenstein, Sarah L / Sota, Teresa L / Rueda, Sergio / Fenta, Haile / Bacon, Jean / Rourke, Sean B

    AIDS care

    2010  Volume 22, Issue 7, Page(s) 793–802

    Abstract: As many as 50% of people living with HIV/AIDS report cognitive difficulties, which can be associated with objective neuropsychological impairments and depression. A number of studies have demonstrated an association between higher social support and ... ...

    Abstract As many as 50% of people living with HIV/AIDS report cognitive difficulties, which can be associated with objective neuropsychological impairments and depression. A number of studies have demonstrated an association between higher social support and lower rates of depression. Using a cross-sectional design, we examined the role social support may play in attenuating the effects of both neuropsychological status and depression on cognitive difficulties. A total of 357 participants completed a battery of neuropsychological tests, questionnaires about cognitive difficulties and depression, and an interview that included an assessment of perceived level of social support. A multivariate linear regression analysis revealed that higher levels of cognitive symptom burden were significantly associated with depression (P<0.05) while lower levels of cognitive symptom burden were significantly associated with greater social support (P<0.01) and higher level of education (P<0.05). There was a significant interaction between neuropsychological status and depression (P<0.001); the presence of neuropsychological impairment with depression was associated with higher levels of cognitive symptom burden. There was also a significant interaction between social support and depression (P<0.05). Interestingly, social support was also associated with a lower cognitive symptom burden for non-depressed individuals living with HIV/AIDS. These findings have important clinical implications for promoting psychological well-being in persons living with HIV/AIDS. To improve quality of life, it is important to screen for and identify individuals with HIV/AIDS who may be depressed and to intervene appropriately. Further research should examine the potential role of social support interventions in modifying the effects of both depression and neuropsychological status on cognitive symptom burden.
    MeSH term(s) Acquired Immunodeficiency Syndrome/psychology ; Adult ; Cognition Disorders/diagnosis ; Cognition Disorders/psychology ; Cost of Illness ; Cross-Sectional Studies ; Depression/diagnosis ; Depression/psychology ; Depression/therapy ; Educational Status ; HIV Infections/psychology ; Humans ; Male ; Middle Aged ; Neuropsychology ; Ontario ; Quality of Life ; Regression Analysis ; Social Support ; Surveys and Questionnaires ; Young Adult
    Language English
    Publishing date 2010-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 1012651-x
    ISSN 1360-0451 ; 0954-0121
    ISSN (online) 1360-0451
    ISSN 0954-0121
    DOI 10.1080/09540120903482994
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Surveillance for antiviral-agent-resistant herpes simplex virus in the general population with recurrent herpes labialis.

    Bacon, Teresa H / Boon, Ron J / Schultz, Margaret / Hodges-Savola, Cheryl

    Antimicrobial agents and chemotherapy

    2002  Volume 46, Issue 9, Page(s) 3042–3044

    Abstract: In a general population survey in the United States, the prevalence of antiviral-agent-resistant herpes simplex virus was very low among more than 1,000 isolates from individuals with an episode of recurrent herpes labialis not treated with topical ... ...

    Abstract In a general population survey in the United States, the prevalence of antiviral-agent-resistant herpes simplex virus was very low among more than 1,000 isolates from individuals with an episode of recurrent herpes labialis not treated with topical antiviral agents. Two isolates had borderline resistance to acyclovir (0.2%), and all were susceptible to penciclovir.
    MeSH term(s) Acyclovir/administration & dosage ; Acyclovir/analogs & derivatives ; Acyclovir/pharmacology ; Acyclovir/therapeutic use ; Administration, Topical ; Adult ; Animals ; Antiviral Agents/pharmacology ; Cells, Cultured ; Drug Resistance, Viral ; Female ; Guanine ; Herpes Labialis/drug therapy ; Herpes Labialis/epidemiology ; Herpes Labialis/virology ; Herpesvirus 1, Human/drug effects ; Humans ; Male ; Population ; Rabbits ; Recurrence ; United States/epidemiology
    Chemical Substances Antiviral Agents ; penciclovir (359HUE8FJC) ; Guanine (5Z93L87A1R) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2002-08-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.46.9.3042-3044.2002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy.

    Bacon, Teresa H / Levin, Myron J / Leary, Jeffry J / Sarisky, Robert T / Sutton, David

    Clinical microbiology reviews

    2001  Volume 16, Issue 1, Page(s) 114–128

    Abstract: Acyclovir, penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections. In spite of the distribution of over 2.3 x 10(6) kg of these nucleoside analogues, the prevalence of acyclovir ... ...

    Abstract Acyclovir, penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections. In spite of the distribution of over 2.3 x 10(6) kg of these nucleoside analogues, the prevalence of acyclovir resistance in herpes simplex virus isolates from immunocompetent hosts has remained stable at approximately 0.3%. In immuncompromised patients, in whom the risk for developing resistance is much greater, the prevalence of resistant virus has also remained stable but at a higher level, typically 4 to 7%. These observations are examined in the light of characteristics of the virus, the drugs, and host factors.
    MeSH term(s) Acyclovir/analogs & derivatives ; Acyclovir/chemistry ; Acyclovir/therapeutic use ; Antiviral Agents/chemistry ; Antiviral Agents/therapeutic use ; Drug Resistance, Viral ; Guanine ; Herpes Simplex/drug therapy ; Herpes Simplex/epidemiology ; Herpes Simplex/physiopathology ; Humans ; Microbial Sensitivity Tests ; Simplexvirus/drug effects
    Chemical Substances Antiviral Agents ; penciclovir (359HUE8FJC) ; Guanine (5Z93L87A1R) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2001-10-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 645015-5
    ISSN 1098-6618 ; 0893-8512
    ISSN (online) 1098-6618
    ISSN 0893-8512
    DOI 10.1128/CMR.16.1.114-128.2003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis.

    Shin, Young Kyoo / Weinberg, Adriana / Spruance, Spotswood / Bernard, Mariann / Bacon, Teresa H / Boon, Ron J / Levin, Myron J

    The Journal of infectious diseases

    2003  Volume 187, Issue 8, Page(s) 1241–1245

    Abstract: Subjects received topical penciclovir for 4 days during successive episodes of recurrent herpes labialis. Isolation of herpes simplex virus (HSV) was attempted from lesions obtained before initiation of treatment and on each day of therapy. Isolates ... ...

    Abstract Subjects received topical penciclovir for 4 days during successive episodes of recurrent herpes labialis. Isolation of herpes simplex virus (HSV) was attempted from lesions obtained before initiation of treatment and on each day of therapy. Isolates remained sensitive to penciclovir when tested by a plaque reduction assay, and there was no significant change in sensitivity during any treatment course or between successive treatments. The proportion of nucleoside-resistant variants present within a subset of these isolates was further investigated using a more-sensitive plating efficiency assay. Although the proportion of antiviral-resistant HSV variants increased on successive days, it invariably remained a minor subpopulation. Moreover, isolates from successive episodes obtained before treatment showed no change in the proportion of resistant HSV variants. We conclude that antiviral-resistant variants, which are readily detected in HSV isolates from peripheral lesions, do not accumulate in the sensory ganglia of immunocompetent patients receiving multiple courses of nucleoside analogues.
    MeSH term(s) Acyclovir/administration & dosage ; Acyclovir/analogs & derivatives ; Acyclovir/pharmacology ; Acyclovir/therapeutic use ; Adolescent ; Adult ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Drug Resistance, Viral ; Female ; Herpes Labialis/drug therapy ; Herpesvirus 1, Human/drug effects ; Humans ; Male ; Time Factors ; Viral Plaque Assay
    Chemical Substances Antiviral Agents ; penciclovir (359HUE8FJC) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2003-04-15
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1086/373993
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Assessor- and participant-blinded, randomized controlled trial of dense cranial electroacupuncture stimulation plus body acupuncture for neuropsychiatric sequelae of stroke.

    Zhang, Zhang-Jin / Zhao, Hong / Jin, Gui-Xing / Man, Sui-Cheung / Wang, Yi-Si / Wang, Ying / Wang, Hai-Rong / Li, Meng-Han / Yam, Lo-Lo / Qin, Zong-Shi / Yu, Kim-Kam Teresa / Wu, Jing / Ng, Fung-Leung Bacon / Ziea, Tat-Chi Eric / Rong, Pei-Jing

    Psychiatry and clinical neurosciences

    2019  Volume 74, Issue 3, Page(s) 183–190

    Abstract: Aim: Acupuncture has benefits in the rehabilitation of neuropsychiatric sequelae of stroke. This study was aimed to evaluate the effectiveness of dense cranial electroacupuncture stimulation plus body acupuncture (DCEAS+BA) in treating poststroke ... ...

    Abstract Aim: Acupuncture has benefits in the rehabilitation of neuropsychiatric sequelae of stroke. This study was aimed to evaluate the effectiveness of dense cranial electroacupuncture stimulation plus body acupuncture (DCEAS+BA) in treating poststroke depression (PSD), functional disability, and cognitive deterioration.
    Methods: In this assessor- and participant-blinded, randomized controlled trial, 91 stroke patients who initially had PSD were randomly assigned to either DCEAS+BA (n = 45) or minimum acupuncture stimulation as controls (n = 46) for three sessions per week over 8 consecutive weeks. The primary outcome was baseline-to-end-point change in score of the 17-item Hamilton Depression Rating Scale. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Barthel Index for functional disability, and the Montreal Cognitive Assessment for cognitive function.
    Results: DCEAS+BA-treated patients showed strikingly greater end-point reduction than MAS-treated patients in scores of the three symptom domains. The clinical response rate, defined as an at least 50% baseline-to-end-point reduction in 17-item Hamilton Depression Rating Scale score, was markedly higher in the DCEAS+BA-treated group than that of controls (40.0% vs 17.4%, P = 0.031). Incidence of adverse events was not different in the two groups. Subgroup analysis revealed that DCEAS+BA with electrical stimulation on forehead acupoints was more apparent in reducing Barthel-Index-measured disability than that without electrical stimulation.
    Conclusion: DCEAS+BA, particularly with electrical stimulation on forehead acupoints, reduces PSD, functional disability, and cognitive deterioration of stroke patients. It can serve as an effective rehabilitation therapy for neuropsychiatric sequelae of stroke.
    MeSH term(s) Acupuncture Points ; Acupuncture Therapy/methods ; Aged ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/rehabilitation ; Depression/etiology ; Depression/rehabilitation ; Double-Blind Method ; Electroacupuncture/methods ; Extremities ; Female ; Forehead ; Humans ; Male ; Middle Aged ; Outcome and Process Assessment, Health Care ; Severity of Illness Index ; Skull ; Stroke/complications ; Stroke/therapy ; Stroke Rehabilitation/methods
    Language English
    Publishing date 2019-12-20
    Publishing country Australia
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 1292906-2
    ISSN 1440-1819 ; 1323-1316
    ISSN (online) 1440-1819
    ISSN 1323-1316
    DOI 10.1111/pcn.12959
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Peripheral T-cell lymphoma with a follicular growth pattern: derivation from follicular helper T cells and relationship to angioimmunoblastic T-cell lymphoma.

    Bacon, Chris M / Paterson, Jennifer C / Liu, Hongxiang / Payne, Karen / Munson, Philippa / Du, Ming-Qing / Marafioti, Teresa

    British journal of haematology

    2008  Volume 143, Issue 3, Page(s) 439–441

    MeSH term(s) Adult ; Germinal Center/pathology ; Humans ; Immunoblastic Lymphadenopathy/immunology ; Lymphoma, T-Cell, Peripheral/immunology ; Male ; T-Lymphocytes, Helper-Inducer/immunology
    Language English
    Publishing date 2008-11
    Publishing country England
    Document type Case Reports ; Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/j.1365-2141.2008.07352.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations.

    Duffy, Karen E / Quail, Matthew R / Nguyen, Tammy T / Wittrock, Robert J / Bartus, Joan O / Halsey, Wendy M / Leary, Jeffry J / Bacon, Teresa H / Sarisky, Robert T

    BMC infectious diseases

    2002  Volume 2, Page(s) 7

    Abstract: Background: The thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80- ... ...

    Abstract Background: The thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1.
    Methods: A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol) within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases.
    Results: Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2-4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed significant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA structure.
    Conclusions: This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a) mutations may be modulated by other viral polypeptides cooperating with Pol, and (b) the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.
    MeSH term(s) Animals ; Biological Assay ; Cell Line ; Cercopithecus aethiops ; DNA Polymerase II/biosynthesis ; DNA Polymerase II/genetics ; DNA Polymerase II/metabolism ; DNA Replication/drug effects ; DNA Replication/genetics ; DNA, Recombinant/genetics ; DNA, Recombinant/metabolism ; DNA, Viral/genetics ; DNA, Viral/metabolism ; DNA-Directed DNA Polymerase/biosynthesis ; DNA-Directed DNA Polymerase/genetics ; DNA-Directed DNA Polymerase/metabolism ; Exodeoxyribonucleases/biosynthesis ; Exodeoxyribonucleases/genetics ; Exodeoxyribonucleases/metabolism ; Genome, Viral ; Herpesvirus 1, Human/enzymology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/metabolism ; Herpesvirus 2, Human/enzymology ; Herpesvirus 2, Human/genetics ; Humans ; Mutagenesis/drug effects ; Mutagenesis/genetics ; Mutation/drug effects ; Mutation/genetics ; Nucleic Acid Conformation/drug effects ; Plasmids/biosynthesis ; Plasmids/genetics ; Thymidine Kinase/genetics ; Thymidine Kinase/metabolism ; Transfection ; Vero Cells/chemistry ; Vero Cells/metabolism ; Viral Proteins/biosynthesis ; Viral Proteins/genetics ; Viral Proteins/metabolism
    Chemical Substances DNA, Recombinant ; DNA, Viral ; Viral Proteins ; Thymidine Kinase (EC 2.7.1.21) ; DNA Polymerase II (EC 2.7.7.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Exodeoxyribonucleases (EC 3.1.-) ; DNA polymerase, Simplexvirus (EC 3.1.11.-)
    Language English
    Publishing date 2002-05-07
    Publishing country England
    Document type Journal Article
    ISSN 1471-2334
    ISSN (online) 1471-2334
    DOI 10.1186/1471-2334-2-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Comparison of methods for identifying resistant herpes simplex virus and measuring antiviral susceptibility.

    Sarisky, Robert T / Crosson, Paul / Cano, Rachel / Quail, Matthew R / Nguyen, Tammy T / Wittrock, Robert J / Bacon, Teresa H / Sacks, Stephen L / Caspers-Velu, Laure / Hodinka, Richard L / Leary, Jeffry J

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

    2001  Volume 23, Issue 3, Page(s) 191–200

    Abstract: Background: A number of in vitro assays are used to determine susceptibility of HSV to antiviral agents, but results from these in vitro assays do not necessarily correlate with treatment outcome.: Objectives: A method with improved capability for ... ...

    Abstract Background: A number of in vitro assays are used to determine susceptibility of HSV to antiviral agents, but results from these in vitro assays do not necessarily correlate with treatment outcome.
    Objectives: A method with improved capability for identifying an isolate as acyclovir (ACV) or penciclovir (PCV) resistant when resistance is borderline could greatly improve the management of HSV disease.
    Study design: A comparative evaluation of four in vitro assays, plaque reduction (PRA), DNA hybridization, plating efficiency (PEA) and plaque autoradiography (PAR) was performed to accurately identify and measure resistance of a TK-altered clinical HSV isolate (HSV-1 N4) from a patient who was non-responsive to ACV treatment. Two established criteria for the prediction of antiviral resistance, IC(50)> or =2.0 microg/ml or an IC(50) greater than 10x above a sensitive virus IC(50), as well as testing in human (MRC-5) and nonhuman (Vero and CV-1 monkey kidney) cell lines were evaluated.
    Results: The PRA and DNA hybridization assays accurately identified HSV-1 N4 as ACV(r) in human cells when using the 10x above sensitive virus IC(50) resistance criterion. Moreover, the PEA and PAR assays failed to classify HSV-1 N4 as drug resistant and indicate that these technologies alone are inadequate for identifying resistant virus.
    Conclusions: The data presented herein indicate that the PRA and DNA hybridization assays most accurately identified an otherwise borderline-resistant isolate as drug resistant: (i) when a sensitive virus is used within each individual assay as a control, (ii) when ACV and PCV susceptibility is evaluated in human cells, and (iii) when the 10x above sensitive IC(50) criterion is used to classify a virus as drug-resistant. Testing of additional clinical samples is warranted to further confirm these findings.
    MeSH term(s) Acyclovir/analogs & derivatives ; Acyclovir/pharmacology ; Antiviral Agents/pharmacology ; Autoradiography ; Drug Resistance, Viral ; Microbial Sensitivity Tests ; Nucleic Acid Hybridization ; Simplexvirus/drug effects ; Simplexvirus/enzymology ; Thymidine Kinase/metabolism ; Viral Plaque Assay
    Chemical Substances Antiviral Agents ; penciclovir (359HUE8FJC) ; Thymidine Kinase (EC 2.7.1.21) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2001-09-11
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article
    ZDB-ID 1446080-4
    ISSN 1873-5967 ; 1386-6532
    ISSN (online) 1873-5967
    ISSN 1386-6532
    DOI 10.1016/s1386-6532(01)00221-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations

    Leary Jeffry J / Halsey Wendy M / Bartus Joan O / Wittrock Robert J / Nguyen Tammy T / Quail Matthew R / Duffy Karen E / Bacon Teresa H / Sarisky Robert T

    BMC Infectious Diseases, Vol 2, Iss 1, p

    2002  Volume 7

    Abstract: Abstract Background The thymidine kinase ( tk ) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- ...

    Abstract Abstract Background The thymidine kinase ( tk ) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1. Methods A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol) within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases. Results Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAA r 5 exhibited a 2–4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed signficant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA stucture. Conclusions This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a) mutations may be modulated by other viral polypeptides cooperating with Pol, and (b) the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.
    Keywords Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 570
    Language English
    Publishing date 2002-05-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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