engleski

Ongoing evolution of a novel Human metapneumovirus subcluster in Croatia

Introduction: Human metapneumovirus (HMPV) is a ubiquitous pathogen of the Pneumoviridae family which causes serious respiratory illness in infants, young children, the elderly, and immunocompromised individuals. Previous reports have shown that the viral attachment glycoprotein (G), one of the major envelope glycoproteins, modulates innate and adaptive immune responses, leading to incomplete immunity and promoting reinfection. Our recent study on genomics of HMPV circulating in Croatia has shown occurrence of a novel virus subcluster A2c within group A genotype. The aim of this study was genetic characterisation of highly diverse G gene of this recently emerged subclaster. Materials and Methods: This study included 49 nasopharyngeal specimens obtained from hospitalized patients with respiratory infections in Croatia (in 2017) shown to be positive for HMPV in direct-fluorescence assay. All samples were genotyped by amplifying and sequencing a 473 nucleotide long region of fusion protein. Further molecular analyses were conducted for strains belonging to subcluster A2c based on the complete sequence of G gene. Results and conclusion: In 2017, A2c subcluster has completely replaced all other group A subclusters and accounted for 75% of infections ih hospitalized patients. To gain more insight into evolution of G gene, we included all A2c strains from previous seasons (2011-2016) in phylodynamic analysis and showed substationally higher evolutionary rate of G gene than previously observed. Further surveillance will clarify if this local rate will follow the observed global trend in the near future. Sequence analysis of complete G gene also showed that this gene is rapidly evolving by gaining two large duplications, either 111 (in 5 of 19 strains) or 180 (in 11 of 19 strains) nucleotides long leading to 37 or 60 amino acid longer G proteins, respectively. Such duplications were recently found within HMPV strains circulating in Spain and Japan. No potential acceptor sites for N-linked sugars have been added by these duplications. Due to heavily glycosylated nature of G gene, estimation of O-glycosylation pattern was not straightforward, but strains containing duplications potentially have more acceptor sites for O-linked glycans. Additionally, amino acid changes were observed between the first and the second copy of the duplicated region further demonstrating ongoing virus evolution in an extremely narrow time frame. Changes in this region may account for the ability of this virus to infect/reinfect hosts either by enhanced attachment specificities or evasion of immune recognition by the host.

human metapneumovirus ; molecular epidemiology ; molecular evolution ; virus variability

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