Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters
| Autor: | Jeanne M. Guzzetta, Mia MacPhail, Roderick Tang, Jasmine Kaur, Richard R. Spaete, Jeanne H. Schickli |
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| Rok vydání: | 2008 |
| Předmět: |
Gene Expression Regulation
Viral Recombinant Fusion Proteins viruses Green Fluorescent Proteins Biology Virus Replication Virus lcsh:Infectious and parasitic diseases Cell Line Viral Proteins Human metapneumovirus Cricetinae Virology Chlorocebus aethiops medicine Animals Humans lcsh:RC109-216 Metapneumovirus Mutation frequency Vero Cells Paramyxoviridae Infections Base Sequence Mesocricetus Research virus diseases Viral Vaccines biology.organism_classification respiratory tract diseases Infectious Diseases medicine.anatomical_structure Viral replication Cell culture Mutation Respiratory tract |
| Zdroj: | Virology Journal Virology Journal, Vol 5, Iss 1, p 69 (2008) |
| ISSN: | 1743-422X |
| Popis: | 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 from challenge with 106 PFU of wild type (wt) hMPV/NL/1/00. Conclusion 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. |
| Databáze: | OpenAIRE |
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