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

AI Article Synopsis

  • Human metapneumovirus (hMPV) can cause severe respiratory illness in vulnerable populations, but there are currently no effective vaccines or preventative treatments available.
  • In a study, researchers created a modified version of hMPV by deleting the M2-2 gene, which showed altered viral replication dynamics and resulted in a weakened virus in hamster models.
  • The findings suggest that this modified virus (rhMPV/DeltaM2-2) may serve as a potential live vaccine candidate against hMPV, indicating the need for further research on the hMPV polymerase complex and the role of M2-2.

Article 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/DeltaM2-2 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/DeltaM2-2 was attenuated compared to rhMPV in the lungs and nasal turbinates of hamsters. Hamsters immunized with one dose of rhMPV/DeltaM2-2 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, rhMPVDeltaM2-2 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426676PMC
http://dx.doi.org/10.1186/1743-422X-5-69DOI Listing

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