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  1. Article ; Online: An attenuated temperature-sensitive strain of cytomegalovirus (tsm5) establishes immunity without development of CD8(+) T cell memory inflation.

    Beswick, Mark / Pachnio, Annette / Al-Ali, Abdulaziz / Sweet, Clive / Moss, Paul A

    Journal of medical virology

    2013  Volume 85, Issue 11, Page(s) 1968–1974

    Abstract: Cytomegalovirus (CMV) is a widely prevalent herpesvirus that is well tolerated by an immune competent host yet establishes a state of chronic infection. The virus is thought to undergo frequent subclinical episodes of reactivation which leads to an ... ...

    Abstract Cytomegalovirus (CMV) is a widely prevalent herpesvirus that is well tolerated by an immune competent host yet establishes a state of chronic infection. The virus is thought to undergo frequent subclinical episodes of reactivation which leads to an unusually large accumulation of CMV-specific CD8(+) T lymphocytes in the peripheral blood, a phenomenon termed "memory inflation." The high magnitude of the CMV T cell response has been implicated in impaired immunity to heterologous pathogens such as EBV, influenza and West Nile virus. Here, using murine CMV (MCMV), we show that memory inflation of virus-specific CD8(+) T cells is avoided if mice are infected with a replication defective virus called temperature-sensitive mutant 5 (tsm5), which carries an attenuating mutation within the DNA primase gene. Mice infected with tsm5 do generate primary T cell responses towards viral proteins but these do not amass to skew the memory repertoire of CD8(+) T cells. Therefore, attenuation of the virus replication machinery may be valuable in future CMV vaccine designs because the virus remains immunogenic but does not contribute to CMV associated T cell immune senescence.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; Cytomegalovirus Vaccines/administration & dosage ; Cytomegalovirus Vaccines/immunology ; Disease Models, Animal ; Female ; Herpesviridae Infections/immunology ; Herpesviridae Infections/virology ; Immunologic Memory ; Mice ; Mice, Inbred C57BL ; Muromegalovirus/immunology ; Muromegalovirus/physiology ; Mutation ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Virulence ; Virus Replication
    Chemical Substances Cytomegalovirus Vaccines ; Vaccines, Attenuated
    Language English
    Publishing date 2013-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 752392-0
    ISSN 1096-9071 ; 0146-6615
    ISSN (online) 1096-9071
    ISSN 0146-6615
    DOI 10.1002/jmv.23688
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antiviral therapy can reverse the development of immune senescence in elderly mice with latent cytomegalovirus infection.

    Beswick, Mark / Pachnio, Annette / Lauder, Sarah N / Sweet, Clive / Moss, Paul A

    Journal of virology

    2012  Volume 87, Issue 2, Page(s) 779–789

    Abstract: Cytomegalovirus (CMV) infection leads to the development of adaptive and humoral immune responses that are among the largest for any pathogen, and intriguingly, the magnitude of the immune response increases with age, a phenomenon termed "memory ... ...

    Abstract Cytomegalovirus (CMV) infection leads to the development of adaptive and humoral immune responses that are among the largest for any pathogen, and intriguingly, the magnitude of the immune response increases with age, a phenomenon termed "memory inflation." Elevated CMV-specific immunity has been correlated with an increased mortality rate in elderly individuals and with impaired vaccination responses. The latent phase of CMV infection is characterized by intermittent episodes of subclinical viral reactivation and the production of immunogenic transcripts that may maintain memory inflation of virus-specific cytotoxic lymphocytes. However, the relative importance of CMV reactivation in the development of memory inflation is uncertain, as is the potential for antiviral treatment to reverse this effect. Here, we administered valaciclovir for up to 12 months in mice with established murine CMV (MCMV) infection. Treatment reduced the magnitude of the MCMV-specific CD8(+) T-lymphocyte response by 80%, and the residual MCMV tetramer-specific lymphocytes exhibited a less differentiated phenotype. In addition, latent MCMV infection suppressed the proportion of naïve CD8(+) T cells by 60% compared to antiviral-treated mice or MCMV-negative animals. Furthermore, treatment led to a reduction in influenza A viral loads following a challenge in elderly MCMV-infected animals and also reduced the differentiation of influenza virus-specific cytotoxic lymphocytes. These observations demonstrate that MCMV-specific memory inflation is maintained by viral replication and that therapeutic intervention could lead to improved immune function.
    MeSH term(s) Acyclovir/administration & dosage ; Acyclovir/analogs & derivatives ; Animals ; Antiviral Agents/administration & dosage ; CD8-Positive T-Lymphocytes/immunology ; Cytomegalovirus Infections/drug therapy ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/veterinary ; Female ; Immunologic Memory ; Mice ; Mice, Inbred C57BL ; Muromegalovirus/immunology ; Muromegalovirus/pathogenicity ; Valacyclovir ; Valine/administration & dosage ; Valine/analogs & derivatives ; Virus Activation ; Virus Latency
    Chemical Substances Antiviral Agents ; Valine (HG18B9YRS7) ; Valacyclovir (MZ1IW7Q79D) ; Acyclovir (X4HES1O11F)
    Language English
    Publishing date 2012-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.02427-12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: CMV and Immunosenescence

    Solana Rafael / Tarazona Raquel / Aiello Allison E / Akbar Arne N / Appay Victor / Beswick Mark / Bosch Jos A / Campos Carmen / Cantisán Sara / Cicin-Sain Luka / Derhovanessian Evelyna / Ferrando-Martínez Sara / Frasca Daniela / Fulöp Tamas / Govind Sheila / Grubeck-Loebenstein Beatrix / Hill Ann / Hurme Mikko / Kern Florian /
    Larbi Anis / López-Botet Miguel / Maier Andrea B / McElhaney Janet E / Moss Paul / Naumova Elissaveta / Nikolich-Zugich Janko / Pera Alejandra / Rector Jerrald L / Riddell Natalie / Sanchez-Correa Beatriz / Sansoni Paolo / Sauce Delphine / van Lier Rene / Wang George C / Wills Mark R / Zieliński Maciej / Pawelec Graham

    Immunity & Ageing, Vol 9, Iss 1, p

    from basics to clinics

    2012  Volume 23

    Abstract: Abstract Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has ... ...

    Abstract Abstract Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16 th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
    Keywords Geriatrics ; RC952-954.6 ; Special situations and conditions ; RC952-1245 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; DOAJ:Allergy and Immunology
    Subject code 610
    Language English
    Publishing date 2012-10-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Report from the second cytomegalovirus and immunosenescence workshop

    Wills Mark / Akbar Arne / Beswick Mark / Bosch Jos A / Caruso Calogero / Colonna-Romano Giuseppina / Dutta Ambarish / Franceschi Claudio / Fulop Tamas / Gkrania-Klotsas Effrossyni / Goronzy Joerg / Griffiths Stephen J / Henson Sian M / Herndler-Brandstetter Dietmar / Hill Ann / Kern Florian / Klenerman Paul / Macallan Derek / Macaulay Richard /
    Maier Andrea B / Mason Gavin / Melzer David / Morgan Matthew / Moss Paul / Nikolich-Zugich Janko / Pachnio Annette / Riddell Natalie / Roberts Ryan / Sansoni Paolo / Sauce Delphine / Sinclair John / Solana Rafael / Strindhall Jan / Trzonkowski Piotr / van Lier Rene / Vescovini Rosanna / Wang George / Westendorp Rudi / Pawelec Graham

    Immunity & Ageing, Vol 8, Iss 1, p

    2011  Volume 10

    Abstract: Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4 th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and ... ...

    Abstract Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4 th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.
    Keywords Geriatrics ; RC952-954.6 ; Special situations and conditions ; RC952-1245 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; DOAJ:Allergy and Immunology
    Language English
    Publishing date 2011-10-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: CMV and Immunosenescence: from basics to clinics.

    Solana, Rafael / Tarazona, Raquel / Aiello, Allison E / Akbar, Arne N / Appay, Victor / Beswick, Mark / Bosch, Jos A / Campos, Carmen / Cantisán, Sara / Cicin-Sain, Luka / Derhovanessian, Evelyna / Ferrando-Martínez, Sara / Frasca, Daniela / Fulöp, Tamas / Govind, Sheila / Grubeck-Loebenstein, Beatrix / Hill, Ann / Hurme, Mikko / Kern, Florian /
    Larbi, Anis / López-Botet, Miguel / Maier, Andrea B / McElhaney, Janet E / Moss, Paul / Naumova, Elissaveta / Nikolich-Zugich, Janko / Pera, Alejandra / Rector, Jerrald L / Riddell, Natalie / Sanchez-Correa, Beatriz / Sansoni, Paolo / Sauce, Delphine / van Lier, Rene / Wang, George C / Wills, Mark R / Zieliński, Maciej / Pawelec, Graham

    Immunity & ageing : I & A

    2012  Volume 9, Issue 1, Page(s) 23

    Abstract: Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been ... ...

    Abstract Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
    Language English
    Publishing date 2012-10-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 2168941-6
    ISSN 1742-4933 ; 1742-4933
    ISSN (online) 1742-4933
    ISSN 1742-4933
    DOI 10.1186/1742-4933-9-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Report from the second cytomegalovirus and immunosenescence workshop.

    Wills, Mark / Akbar, Arne / Beswick, Mark / Bosch, Jos A / Caruso, Calogero / Colonna-Romano, Giuseppina / Dutta, Ambarish / Franceschi, Claudio / Fulop, Tamas / Gkrania-Klotsas, Effrossyni / Goronzy, Joerg / Griffiths, Stephen J / Henson, Sian / Herndler-Brandstetter, Dietmar / Hill, Ann / Kern, Florian / Klenerman, Paul / Macallan, Derek / Macualay, Richard /
    Maier, Andrea B / Mason, Gavin / Melzer, David / Morgan, Matthew / Moss, Paul / Nikolich-Zugich, Janko / Pachnio, Annette / Riddell, Natalie / Roberts, Ryan / Sansoni, Paolo / Sauce, Delphine / Sinclair, John / Solana, Rafael / Strindhall, Jan / Trzonkowski, Piotr / van Lier, Rene / Vescovini, Rosanna / Wang, George / Westendorp, Rudi / Pawelec, Graham

    Immunity & ageing : I & A

    2011  Volume 8, Issue 1, Page(s) 10

    Abstract: The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; ...

    Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.
    Language English
    Publishing date 2011-10-28
    Publishing country England
    Document type Editorial
    ZDB-ID 2168941-6
    ISSN 1742-4933 ; 1742-4933
    ISSN (online) 1742-4933
    ISSN 1742-4933
    DOI 10.1186/1742-4933-8-10
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: CMV and Immunosenescence

    Solana, Rafael / Tarazona, Raquel / Aiello, Allison E / Akbar, Arne N / Appay, Victor / Beswick, Mark / Bosch, Jos A / Campos, Carmen / Cantisán, Sara / Cicin-Sain, Luka / Derhovanessian, Evelyna / Ferrando-Martínez, Sara / Frasca, Daniela / Fulöp, Tamas / Govind, Sheila / Grubeck-Loebenstein, Beatrix / Hill, Ann / Hurme, Mikko / Kern, Florian /
    Larbi, Anis / López-Botet, Miguel / Maier, Andrea B / McElhaney, Janet E / Moss, Paul / Naumova, Elissaveta / Nikolich-Zugich, Janko / Pera, Alejandra / Rector, Jerrald L / Riddell, Natalie / Sanchez-Correa, Beatriz / Sansoni, Paolo / Sauce, Delphine / van Lier, Rene / Wang, George C / Wills, Mark R / Zieliński, Maciej / Pawelec, Graham

    from basics to clinics.

    2012  

    Abstract: Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been ... ...

    Abstract Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: CMV and Immunosenescence

    Solana, Rafael / Tarazona, Raquel / Aiello, Allison E / Akbar, Arne N / Appay, Victor / Beswick, Mark / Bosch, Jos A / Campos, Carmen / Cantisán, Sara / Cicin-Sain, Luka / Derhovanessian, Evelyna / Ferrando-Martínez, Sara / Frasca, Daniela / Fulöp, Tamas / Govind, Sheila / Grubeck-Loebenstein, Beatrix / Hill, Ann / Hurme, Mikko / Kern, Florian /
    Larbi, Anis / López-Botet, Miguel / Maier, Andrea B / McElhaney, Janet E / Moss, Paul / Naumova, Elissaveta / Nikolich-Zugich, Janko / Pera, Alejandra / Rector, Jerrald L / Riddell, Natalie / Sanchez-Correa, Beatriz / Sansoni, Paolo / Sauce, Delphine / van Lier, Rene / Wang, George C / Wills, Mark R / Zieliński, Maciej / Pawelec, Graham

    from basics to clinics.

    2012  

    Abstract: Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been ... ...

    Abstract Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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