Human metapneumovirus - what we know now [version 1; referees: 2 approved]

F1000Research 2018, 7(F1000 Faculty Rev):135 Last updated: 31 MAR 2022 REVIEW Human metapneumovirus - what we know now [version 1; peer review: 2 approved] Nazly Shafagati, John Williams Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA v1 First published: 01 Feb 2018, 7(F1000 Faculty Rev):135 https://doi.org/10.12688/f1000research.12625.1 Open Peer Review Latest published: 01 Feb 2018, 7(F1000 Faculty Rev):135 https://doi.org/10.12688/f1000research.12625.1 Approval Status 1 Abstract Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response. Keywords human metapneumovirus, acute respiratory infection, Viral pneumonia 2 version 1 01 Feb 2018 Faculty Reviews are review articles written by the prestigious Members of Faculty Opinions. The articles are commissioned and peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. 1. Xiaoyong Bao, University of Texas Medical Branch, Galveston, USA 2. Jianrong Li, College of Veterinary Medicine, The Ohio State University, , Ohio, USA Any comments on the article can be found at the end of the article. Page 1 of 11 F1000Research 2018, 7(F1000 Faculty Rev):135 Last updated: 31 MAR 2022 Corresponding author: John Williams () Author roles: Shafagati N: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Williams J: Conceptualization, Funding Acquisition, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests: JVW serves on a Scientific Advisory Board of Quidel and an Independent Data Monitoring Committee for GlaxoSmithKline. NS has no competing interests. Grant information: JVW was supported by National Institutes of Health grant R01 AI-085062. NS was supported by National Institutes of Health grant T32 AI060525. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2018 Shafagati N and Williams J. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Shafagati N and Williams J. Human metapneumovirus - what we know now [version 1; peer review: 2 approved] F1000Research 2018, 7(F1000 Faculty Rev):135 https://doi.org/10.12688/f1000research.12625.1 First published: 01 Feb 2018, 7(F1000 Faculty Rev):135 https://doi.org/10.12688/f1000research.12625.1 Page 2 of 11 F1000Research 2018, 7(F1000 Faculty Rev):135 Last updated: 31 MAR 2022 Introduction The start of the twenty-first century has seen the discovery of several emerging or new respiratory pathogens causing human disease, including severe acute respiratory syndrome coronavirus and human metapneumovirus (HMPV). The metapneumoviruses are enveloped, non-segmented, negative-sense, single-stranded RNA viruses1. They comprise a genus of two species: avian metapneumovirus and HMPV. The metapneumoviruses belong to the order Mononegavirales and family Pneumoviridae, which also includes respiratory syncytial virus (RSV)2,3. serotype C (up to 88% homology). However the newly discovered virus replicated efficiently in monkeys but not in birds2. Archived sera from the 1950s contained neutralizing antibodies against HMPV2. Two retrospective Canadian studies detected HMPV in specimens collected from patients with respiratory illness between 1993 and 20019,10, and a US study detected HMPV in specimens from 1976 to 200111. Collectively, these studies show that HMPV has been circulating undetected for many decades. Genome organization and structure Avian metapneumovirus Avian metapneumovirus (previously known as turkey rhinotracheitis virus) was discovered in 1978 in turkeys in South Africa4. Since then, the virus has been recognized to infect turkeys, chickens, and ducks worldwide with a significant economic impact5. The virus has a low and variable mortality but high morbidity rate (up to 100%) and causes severe upper respiratory infections as well reproductive issues leading to decreased egg production5. There are currently four subtypes of avian metapneumovirus based on the genetic diversity of the attachment (G) protein6. Subtype A was first isolated in South Africa, followed by subtype B in several European countries. Subtype C was discovered in the US in 19967, and subtype D was identified in France in 20008. It is thought that wild migratory birds play a key role in the spread of avian metapneumovirus5. Discovery of human metapneumovirus In 2001, researchers in the Netherlands first identified HMPV from stored nasopharyngeal samples from 28 children with respiratory illness by using electron microscopy and random reverse transcription-polymerase chain reaction (RT-PCR) techniques. This novel virus exhibited cytopathic effect but not hemadsorption in tertiary monkey kidney epithelial cells. The genome was most closely related to avian metapneumovirus HMPV is a negative-sense, non-segmented, single-stranded RNA virus. The genome is about 13,000 nucleotides in length and is composed of eight genes encoding for nine proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), matrix-2 proteins (M2-1 and M2-2), small hydrophobic (SH) protein, glycoprotein (G), and large (L) polymerase protein (Table 1)12–21. As in other paramyxoviruses, the N, L, and P proteins form the viral replication complex. Though similar in genome to RSV, both avian metapneumovirus and HMPV possess a gene order different from that of RSV and lack the non-structural proteins NS1 and NS21. HMPV exhibits a paramyxovirus-like morphology, ranging from 150 to 600 nm in size, enveloped with short (...truncated)