Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-06-01
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| Series: | Virology Journal |
| Online Access: | http://www.virologyj.com/content/5/1/69 |
| _version_ | 1818359441907515392 |
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| author | Guzzetta Jeanne M MacPhail Mia Kaur Jasmine Schickli Jeanne H Spaete Richard R Tang Roderick S |
| author_facet | Guzzetta Jeanne M MacPhail Mia Kaur Jasmine Schickli Jeanne H Spaete Richard R Tang Roderick S |
| author_sort | Guzzetta Jeanne M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro </it>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. <it>In vivo</it>, 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 from challenge with 10<sup>6 </sup>PFU of wild type (<it>wt) </it>hMPV/NL/1/00.</p> <p>Conclusion</p> <p>Our results suggest that hMPV M2-2 alters regulation of transcription and influences the fidelity of the polymerase complex during viral genome replication. In the hamster model, rhMPVΔM2-2 is attenuated and protective suggesting that deletion of M2-2 may result in a potential live vaccine candidate. A more thorough knowledge of the hMPV polymerase complex and the role of M2-2 during hMPV replication are being studied as we develop a potential live hMPV vaccine candidate that lacks M2-2 expression.</p> |
| first_indexed | 2024-12-13T20:44:57Z |
| format | Article |
| id | doaj.art-b651d488137b43e5bc295d3af0a807bf |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-12-13T20:44:57Z |
| publishDate | 2008-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-b651d488137b43e5bc295d3af0a807bf2022-12-21T23:32:02ZengBMCVirology Journal1743-422X2008-06-01516910.1186/1743-422X-5-69Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamstersGuzzetta Jeanne MMacPhail MiaKaur JasmineSchickli Jeanne HSpaete Richard RTang Roderick S<p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro </it>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. <it>In vivo</it>, 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 from challenge with 10<sup>6 </sup>PFU of wild type (<it>wt) </it>hMPV/NL/1/00.</p> <p>Conclusion</p> <p>Our results suggest that hMPV M2-2 alters regulation of transcription and influences the fidelity of the polymerase complex during viral genome replication. In the hamster model, rhMPVΔM2-2 is attenuated and protective suggesting that deletion of M2-2 may result in a potential live vaccine candidate. A more thorough knowledge of the hMPV polymerase complex and the role of M2-2 during hMPV replication are being studied as we develop a potential live hMPV vaccine candidate that lacks M2-2 expression.</p>http://www.virologyj.com/content/5/1/69 |
| spellingShingle | Guzzetta Jeanne M MacPhail Mia Kaur Jasmine Schickli Jeanne H Spaete Richard R Tang Roderick S Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters Virology Journal |
| title | Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters |
| title_full | Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters |
| title_fullStr | Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters |
| title_full_unstemmed | Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters |
| title_short | Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters |
| title_sort | deletion of human metapneumovirus m2 2 increases mutation frequency and attenuates growth in hamsters |
| url | http://www.virologyj.com/content/5/1/69 |
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