Cytomegalovirus

Publication Title: 
Nihon Rinsho. Japanese Journal of Clinical Medicine

Medicinal herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula, and Rhus javanica, with anti-herpes simplex virus therapeutic activity, inhibited replication of human cytomegalovirus(CMV) and murine CMV(MCMV) in vitro. These anti-CMV activities were examined in an MCMV infection model using immunosuppressed mice. Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment.

Author(s): 
Shiraki, K.
Yukawa, T.
Kurokawa, M.
Kageyama, S.
Publication Title: 
Age (Dordrecht, Netherlands)

The low percentages of naÔve T cells commonly observed in elderly people are thought to be causally associated with mortality, primarily from infectious disease, and are taken as a hallmark of "immunosenescence". Whether low levels of naive cells actually do associate with mortality has, however, not been tested in longitudinal studies. Here, we present correlations between peripheral T-cell phenotypes and 8-year survival in individuals from the population-based prospective Leiden 85-plus Study.

Author(s): 
Derhovanessian, Evelyna
Maier, Andrea B.
H‰hnel, Karin
Zelba, Henning
de Craen, Anton J. M.
Roelofs, Helene
Slagboom, Eline P.
Westendorp, Rudi G. J.
Pawelec, Graham
Publication Title: 
Experimental Gerontology

Telomere length and telomerase activity have received increased attention as markers of cellular aging, but the determinants of inter-individual variation in these markers are incompletely understood. Cytomegalovirus (CMV) infection may be particularly important for telomere and telomerase dynamics due to its dramatic impact on peripheral blood lymphocyte composition, i.e., increasing the number and proportions of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA).

Author(s): 
Dowd, Jennifer B.
Bosch, Jos A.
Steptoe, Andrew
Blackburn, Elizabeth H.
Lin, Jue
Rees-Clayton, Erin
Aiello, Allison E.
Publication Title: 
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

This is the first report of treatment of cytomegalovirus infection with artesunate, for a stem cell transplant recipient with a newly identified foscarnet-resistant and ganciclovir-resistant DNA polymerase L776M mutation. Artesunate treatment resulted in a 1.7-2.1-log reduction in viral load by treatment day 7, with a viral half-life of 0.9-1.9 days, indicating a highly effective block in viral replication.

Author(s): 
Shapira, Michael Y.
Resnick, Igor B.
Chou, Sunwen
Neumann, Avidan U.
Lurain, Nell S.
Stamminger, Thomas
Caplan, Orit
Saleh, Niveen
Efferth, Thomas
Marschall, Manfred
Wolf, Dana G.
Publication Title: 
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

Traditional Chinese medicine commands a unique position among all traditional medicines because of its 5000 years of history. Our own interest in natural products from traditional Chinese medicine was triggered in the 1990s, by artemisinin-type sesquiterpene lactones from Artemisia annua L. As demonstrated in recent years, this class of compounds has activity against malaria, cancer cells, and schistosomiasis.

Author(s): 
Efferth, Thomas
Romero, Marta R.
Wolf, Dana G.
Stamminger, Thomas
Marin, Jose J. G.
Marschall, Manfred
Publication Title: 
PloS One

BACKGROUND: Artesunate, an artemisinin-derived monomer, was reported to inhibit Cytomegalovirus (CMV) replication. We aimed to compare the in-vitro anti-CMV activity of several artemisinin-derived monomers and newly synthesized artemisinin dimers. METHODS: Four artemisinin monomers and two novel artemisinin-derived dimers were tested for anti-CMV activity in human fibroblasts infected with luciferase-tagged highly-passaged laboratory adapted strain (Towne), and a clinical CMV isolate. Compounds were evaluated for CMV inhibition and cytotoxicity.

Author(s): 
Arav-Boger, Ravit
He, Ran
Chiou, Chuang-Jiun
Liu, Jianyong
Woodard, Lauren
Rosenthal, Andrew
Jones-Brando, Lorraine
Forman, Michael
Posner, Gary
Publication Title: 
Antiviral Research

The anti-malaria drug artesunate has been shown to be an effective inhibitor of cytomegalovirus (CMV) in vitro, in an experimental animal model, and in a recent single-case clinical use. In this first case-series of 6 stem cell transplant recipients who received preemptive artesunate treatment for CMV infection, we have examined the viral kinetics following institution of artesunate, and employed first-phase viral kinetics studies to calculate its antiviral effectiveness.

Author(s): 
Wolf, Dana G.
Shimoni, Avichai
Resnick, Igor B.
Stamminger, Thomas
Neumann, Avidan U.
Chou, Sunwen
Efferth, Thomas
Caplan, Orit
Rose, Jessica
Nagler, Arnon
Marschall, Manfred
Publication Title: 
PloS One

We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4) are significantly more potent in inhibiting human cytomegalovirus (CMV) replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication.

Author(s): 
He, Ran
Mott, Bryan T.
Rosenthal, Andrew S.
Genna, Douglas T.
Posner, Gary H.
Arav-Boger, Ravit
Publication Title: 
Antimicrobial Agents and Chemotherapy

We previously reported that among a series of artemisinin-derived monomers and dimers, dimer diphenyl phosphate (838) was the most potent inhibitor of human cytomegalovirus (CMV) replication. Our continued investigation of a prototypic artemisinin monomer (artesunate [AS]) and dimer (838) now reveals that both compounds have specific activity against CMV but do not inhibit lytic replication of human herpesvirus 1 or 2 or Epstein-Barr virus.

Author(s): 
He, Ran
Park, Kyoungsook
Cai, Hongyi
Kapoor, Arun
Forman, Michael
Mott, Bryan
Posner, Gary H.
Arav-Boger, Ravit
Publication Title: 
Bioorganic & Medicinal Chemistry

We recently reported the anti-cancer and anti-cytomegalovirus (CMV) activity of artemisinin-derived trioxane diphenylphosphate dimer 838. To probe the relationship between chemical structure and anti-CMV and anti-cancer activities, we now report synthesis and evaluation of a series of eight new dimer phosphate ester analogs of 838. This series of novel molecules was screened against human foreskin fibroblasts (HFFs) infected with CMV and against the human Jurkat T cell acute lymphoblastic leukemia cell line.

Author(s): 
Mott, Bryan T.
He, Ran
Chen, Xiaochun
Fox, Jennifer M.
Civin, Curt I.
Arav-Boger, Ravit
Posner, Gary H.

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