J Exp Med. The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a {gamma}{delta} T cell population in humanized mice

[Giuseppe]

[Source: Journal of Experimental Medicine, full text: (LINK). Abstract, edited.]

The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a {gamma}{delta} T cell population in humanized mice



‎Tu, W., Zheng, J., Liu, Y., Sia, S. F., Liu, M., Qin, G., Ng, I. H. Y., Xiang, Z., Lam, K.-T., Peiris, J. S. M., Lau, Y.-L.

There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human V9V2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus?infected cells and inhibit viral replication in vitro. In Rag2<SUP>?/?</SUP>c<SUP>?/?</SUP> immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus?infected Rag2<SUP>?/?</SUP>c<SUP>?/?</SUP> mice reconstituted with V9V2 T cell?depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget?s disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.
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[tetano]

Bone drug can combat flu viruses

Bone drug can combat flu viruses

Researchers at the University Of Hong Kong have discovered that a drug used to treat bone diseases is effective against influenza viruses such as H1N1 swine flu or bird flu. The drug, called pamidronate, can kill the virus by boosting the human immune system. The research is now at a pre-clinical stage and will be extended to human clinical trials. The study has just been published in the Journal of Experimental Medicine.

http://rthk.hk/rthk/news/englishnews/20110629/news_20110629_56_766114.htm

 

[tetano]

Re: Bone drug can combat flu viruses

Re: Bone drug can combat flu viruses

The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice


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Published June 27, 2011
The Rockefeller University Press, doi: 10.1084/jem.20110226
© 2011 Tu et al.

Article

The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice

Wenwei Tu1,3,
Jian Zheng1,
Yinping Liu1,
Sin Fun Sia2,
Ming Liu4,
Gang Qin1,
Iris H.Y. Ng1,2,
Zheng Xiang1,
Kwok-Tai Lam1,
J.S. Malik Peiris2, and
Yu-Lung Lau1

+ Author Affiliations

1Department of Paediatrics and Adolescent Medicine and 2Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
3Joint Research Center of West China Second University Hospital, Sichuan University, 610041 Chengdu, China
4Guangzhou Institute of Respiratory Diseases, Guangzhou Medical College, 510182 Guangzhou, China

CORRESPONDENCE Wenwei Tu: wwtu@hku.hk OR J.S. Malik Peiris: malik@hkucc.hku.hk OR Yu-Lung Lau: lauylung@hkucc.hku.hk

Abstract

There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus–infected cells and inhibit viral replication in vitro. In Rag2−/−γc−/− immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus–infected Rag2−/−γc−/− mice reconstituted with Vγ9Vδ2 T cell–depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget’s disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.

http://jem.rupress.org/content/earl...ract?sid=a08bf661-d612-4d03-847d-30dc19bcdcea