Abstract
Human metapneumovirus (hMPV) is an important pathogen that causes upper and lower respiratory tract infections in children worldwide. hMPV has two major genotypes, hMPV-A and hMPV-B. Epidemiological studies have shown that the two hMPV genotypes alternate in predominance worldwide in recent years. Co-circulation of the two genotypes of hMPV was usually observed and there is no study about the interaction between them, such as competitive replication, which maybe the possible mechanisms for alternating prevalence of subtypes. Our present study have used two different genotypes of hMPV (genotype A: NL/1/00; B: NL/1/99) in different proportions in animal model (BALB/c mice) and cell model (Vero-E6) separately. The result showed that the competitive growth does exist in BALB/c mice, genotype B had a strong competitive advantage. However, genotype B did not cause more severe disease than non-predominant (genotype A) or mixed strains in the study, which were evaluated by the body weight, airway hyperresponsiveness and lung pathology of mouse. In cell model, competitive growth and the two genotypes alternately prevalence were observed. In summary, we confirmed that there was a competitive replication between hMPV genotype A and B, and no difference in disease severity caused by the two subtypes. This study shows a new insight to understand the alternation of hMPV genotype prevalence through genotype competition and provide experimental evidence for disease control and vaccine design.
Highlights
Www.nature.com/scientificreports genotypes of Human metapneumovirus (hMPV) shows similar properties11. hMPV is a negative sense, single-stranded RNA virus with a genome that is approximately 13 kb in length that encodes eight genes and nine proteins, including the following genes and proteins, respectively: N, nucleocapsid; P, phosphoprotein; M, matrix; F, fusion; SH, small hydrophobic; G, glycoprotein; and L, polymerase and M2-1 and M2-2
Theo P et al reported that hMPV subtype A was predominant in 2001–2003, but this shifted to subtype B in 2004 in Queensland, Australia[21]; Wuhua Kong found that genotype A prevailed in the epidemic seasons in 2008–2009 and 2012–2013, while genotype B prevailed in 2009 in Wuhan, China[22]; an article published in Korea in 2016 about an epidemic of hMPV showed that genotype A2a was predominant in 2007 and 2010, genotype B1 was predominant in 2012, and B2 was predominant in 2008 and 2009 and further predicted that genotype A2a would be the predominant hMPV type in 2014 or 2015 in Korea[23]
Most studies of the alternation of the A/B strains during epidemics have been focused on clinical investigations of hMPV strains isolated from symptomatic patients that involved genotyping and statistical analysis, and there was no basic experimental evidence[29,30,31]; We set our study in animal model (BALB/c mice) and cell model (Vero-E6) separately with two different genotypes of hMPV in different proportions
Summary
Www.nature.com/scientificreports genotypes of hMPV shows similar properties11. hMPV is a negative sense, single-stranded RNA virus with a genome that is approximately 13 kb in length that encodes eight genes and nine proteins, including the following genes and proteins, respectively: N, nucleocapsid; P, phosphoprotein; M, matrix; F, fusion; SH, small hydrophobic; G, glycoprotein; and L, polymerase and M2-1 and M2-2. Epidemiological surveys conducted in many countries, such as China, the USA, France, Australia, Italy, Korea, Brazil, and India, have indicated that strains from both major hMPV groups co-circulate within the same community and that the predominant subgroup shifts progressively from one group to another. Many epidemiological studies have found that A/B genotyping indicated a change in the predominant viral genotype over one to three years[2,14,15,16,17,18,19,20]. Co-circulation of the two genotypes of hMPV was usually observed and the interactions between them such as competitive growth might play a role in the formation of alternation[22,27,28]. This research could offer a new opinion to study alternation of genotype prevalence. Our findings provide important information for treatment research, vaccine development, prevention strategies, and the monitoring of outbreaks of hMPV infection
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