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

• Published in: Virology journal Vol. 5; no. 1; p. 69
• Main Authors: Schickli, Jeanne H, Kaur, Jasmine, MacPhail, Mia, Guzzetta, Jeanne M, Spaete, Richard R, Tang, Roderick S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.06.2008; BioMed Central; BMC
• Subjects: Animals; Base Sequence; Cell Line; Cercopithecus aethiops; Cricetinae; Gene Expression Regulation, Viral; Genetic aspects; Genetic transcription; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Health aspects; Human metapneumovirus; Humans; Mesocricetus; Metapneumovirus - genetics; Metapneumovirus - growth & development; Metapneumovirus - physiology; Mutation; Paramyxoviridae Infections - virology; Paramyxoviruses; Prevention; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Risk factors; RNA virus infections; Vero Cells; Viral Proteins - genetics; Viral Proteins - metabolism; Viral Vaccines - administration & dosage; Virus Replication; United States
• DOI: 10.1186/1743-422X-5-69
• ISSN: 1743-422X

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. 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. 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.