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

Jeanne H Schickli1, Jasmine Kaur, Mia Macphail

  • 1Research Dept, MedImmune, Mountain View, CA 94043, USA. Schicklij@medimmune.com

Virology Journal
|June 4, 2008
PubMed
Abstract

Insights

Deleting the M2-2 gene from human metapneumovirus (hMPV) created an attenuated virus. This modified hMPV (rhMPV/DeltaM2-2) protected hamsters against wild-type hMPV infection, suggesting its potential as a live vaccine candidate.

Area of Science:

  • Virology
  • Immunology
  • Vaccine Development

Background:

  • Human metapneumovirus (hMPV) causes severe respiratory illness in vulnerable populations.
  • No licensed preventative measures currently exist for hMPV infections.
  • Research focuses on developing novel strategies against hMPV.

Purpose of the Study:

  • To investigate the role of the M2-2 gene in hMPV replication.
  • To evaluate the potential of a modified hMPV lacking M2-2 as a vaccine candidate.

Main Methods:

  • A variant hMPV lacking the M2-2 gene (rhMPV/DeltaM2-2) was created.
  • Replication of rhMPV/DeltaM2-2 was assessed in vitro and in vivo (hamster model).
  • Viral transcription, genomic RNA, and polymerase complex activity were analyzed.

Main Results:

  • In vitro, M2-2 deletion altered viral transcription and RNA nucleotide insertion.
  • In vivo, rhMPV/DeltaM2-2 showed significant attenuation in hamsters.
  • A single dose of rhMPV/DeltaM2-2 conferred protection against wild-type hMPV challenge.

Conclusions:

  • The M2-2 gene influences hMPV transcription regulation and polymerase fidelity.
  • rhMPV/DeltaM2-2 is attenuated and demonstrates protective immunity in a hamster model.
  • Deletion of M2-2 presents a promising strategy for developing a live hMPV vaccine.

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