Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters.docVIP

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Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters.doc

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Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters

Virology Journal BioMedCentral Research Open Access Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters Jeanne H Schickli*, Jasmine Kaur, Mia MacPhail, Jeanne M Guzzetta, Richard R Spaete and Roderick S Tang Address: Research Dept, MedImmune, Mountain View, CA 94043, USA Email: Jeanne H Schickli* - Schicklij@; Jasmine Kaur - Kaurj@; Mia MacPhail - Macphailm@; Jeanne M Guzzetta - Guzzettaj@; Richard R Spaete - Spaeter@; Roderick S Tang - Tangr@ * Corresponding author Published: 3 June 2008 Received: 16 March 2008 Accepted: 3 June 2008 Virology Journal 2008, 5:69 doi:10.1186/1743-422X-5-69 This article is available from: /content/5/1/69 ? 2008 Schickli et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Human metapneumovirus (hMPV) infection can cause acute lower respiratory tract illness in infants, the immunocompromised, and the elderly. Currently there are no licensed preventative measures for hMPV infections. Using a variant of hMPV/NL/1/00 that does not require trypsin supplementation for growth in tissue culture, we deleted the M2-2 gene and evaluated the replication of rhMPV/ΔM2-2 virus in vitro and in vivo. Results: In vitro studies showed that the ablation of M2-2 increased the propensity for insertion of U nucleotides in poly-U tracts of the genomic RNA. In addition, viral transcription was up-regulated although the level of genomic RNA remained comparable to rhMPV. Thus, deletion of M2-2 alters the ratio between hMPV genome copies and transcripts. In vivo, rhMPV/ΔM2-2 was attenuated compared to rhMPV in the lungs and nasal turbinates of hamsters. Hamsters immunized with one dose of rhMPV/ΔM2-2 were protected fro