Virus Infection Recognition and Early Innate Responses to Non-Enveloped Viral Vectors 英文参考文献.docVIP

Viruses 2010, 2, 244-261; doi:10.3390/v2010244 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Virus Infection Recognition and Early Innate Responses to Non-Enveloped Viral Vectors Dmitry M. Shayakhmetov Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA; E-Mail: dshax@; Tel.: +1-206-543-6773; Fax: +1-206-685-8675 Received: 20 October 2009; in revised form: 13 January 2010 / Accepted: 14 January 2010 / Published: 19 January 2010 Abstract: Numerous human genetic and acquired diseases could be corrected or ameliorated if viruses are harnessed to safely and effectively deliver therapeutic genes to diseased cells and tissues in vivo. Innate immune and inflammatory response represents one of the key stumbling blocks during the development of viral-based therapies. In this review, current data on the early innate immune responses to viruses and to the most commonly used gene therapy vectors (using adenovirus and adeno-associated virus) will be discussed. Recent findings in the field may help develop new approaches to moderate these innate immune anti-viral responses and thus improve the safety of viral vectors for human gene therapy applications. Keywords: virus vectors; innate immunity; inflammation 1. Introduction During the millions of years of co-evolution, viral pathogens and their hosts evolved to an equilibrium allowing both hosts and viruses to coexist and thus survive. However, this equilibrium is quasi-stationary due to constant adaptation of viruses to existing or new hosts and to eternal selection within these hosts for the most effective antiviral mechanisms. One of the best testaments to the quasi- stationary nature of the balance between viruses and their hosts is a set of recent reports of unanticipated severe innate immune and inflammatory responses to rather benign viral pathoge