RNAi Targeting of Human Metapneumovirus <b><i>P</i></b> and <b><i>N</i></b> Genes Inhibits Viral Growth

Abstract

Background/Aims: Human metapneumovirus (hMPV) is an important human respiratory pathogen and is implicated in an array of respiratory illnesses, ranging from asymptomatic infection to severe bronchiolitis. Currently, there is no reliable vaccine or specific antiviral therapy for hMPV infection and treatment is supportive. The use of ribonucleic acid interference has the potential to change that with the targeting of essential viral genes via small interfering RNAs (siRNAs) offering the ability to directly and rapidly treat viral infections. Method: The human lung carcinoma epithelial cell line, A549, was transfected with siRNAs targeting the N and P genes before infecting with hMPV A2 CAN97-83. Viral growth inhibition was then measured by the viral plaque assay and nucleoprotein (N) and phosphoprotein (P) gene knockdown was determined by real-time PCR. Results: In vitro prophylactic use of siRNAs targeting the 3′-abundantly expressed N and P genes of hMPV resulted in potent, sequence-specific viral inhibition. The viral inhibition was specific and not mediated by an anti-viral interferon-β response or cell death. Conclusion: The findings presented here confirmed the highly potent, sequence-specific antiviral effect of siRNAs targeting the N and P gene of hMPV. These results may facilitate the development of a novel therapeutic agent for hMPV control.

Respiratory Virus Infections of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient

“…21,139 An early but perhaps promising area of HMPV drug discovery research is the novel use of small interfering RNAs. 140…”

Human Metapneumovirus: A Largely Unrecognized Threat to Human Health

“…For example, the peptide HRA2 (derived from a heptad repeat domain of the HMPV F protein) was shown to significantly reduce viral loads in animal studies [49]. Additionally, small interfering RNAs have been used to block HMPV infections [50,51]. Intravenous immune globulin (IVIG) or HMPV-specific monoclonal antibodies could potentially be used to neutralize HMPV [52], but their benefits as treatment options for HMPV disease have not been proven.…”