Ultrastructural and Functional Characterization of Mitochondrial Dynamics Induced by Human Respiratory Syncytial Virus Infection in HEp-2 Cells.

Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory tract infections in children under five years of age and older adults worldwide. During hRSV infection, host cells undergo changes in endomembrane organelles, including mitochondria. This organelle is responsible for energy production in the cell and plays an important role in the antiviral response. The present study focuses on characterizing the ultrastructural and functional changes during hRSV infection using thin-section transmission electron microscopy and RT-qPCR. Here we report that hRSV infection alters mitochondrial morphodynamics by regulating the expression of key genes in the antiviral response process, such as Mfn1, VDAC2, and PINK1. Our results suggest that hRSV alters mitochondrial morphology during infection, producing a mitochondrial phenotype with shortened cristae, swollen matrix, and damaged membrane. We also observed that hRSV infection modulates the expression of the aforementioned genes, possibly as an evasion mechanism in the face of cellular antiviral response. Taken together, these results advance our knowledge of the ultrastructural alterations associated with hRSV infection and might guide future therapeutic efforts to develop effective antiviral drugs for hRSV treatment.

Global Extension and Predominance of Human Metapneumovirus A2 Genotype with Partial G Gene Duplication.

Human metapneumovirus (HMPV) is an important respiratory pathogen and is divided in two main groups (A and B). HMPV strains with partial duplications (111-nt and 180-nt duplication) of the G gene have been reported in recent years. Since the initial reports, viruses with these characteristics have been reported in several countries. We analyzed all complete HMPV G gene ectodomain sequences available at GenBank to determine if viruses with 111-nt or 180-nt duplication have become the leading HMPV strains worldwide, and to describe their temporal and geographic distribution. We identified 1462 sequences that fulfilled study criteria (764 HMPV A and 698 HMPV B) reported from 37 countries. The most frequent HMPV A genotype was A2b2 (n = 366), and the most frequent B genotype was B2 (n = 374). A total of 84 sequences contained the 111-nt duplication, and 90 sequences contained the 180-nt duplication. Since 2016, viruses with a partial duplication comprise the most frequent HMPV A sequences globally and have displaced other HMPV A viruses in Asia, Europe, and South America; no sequences of viruses with partial duplication have been reported in North America or Africa so far. Continued surveillance of HMPV is required to identify the emergence and spread of epidemiologically relevant variants.

Global distribution of respiratory syncytial virus A and B infections: a systematic review.

Respiratory syncytial virus (RSV) is the main cause of severe respiratory infections in young children. The need for global epidemiologic data regarding RSV has been increasingly recognized. RSV A infections are reported more frequently than RSV B. Nonetheless, the temporal distribution of infections caused by both RSV groups has not been investigated globally. A systematic review was carried out regarding published studies on RSV A and B epidemiology, as well as RSV G gene ectodomain sequence data available at GenBank. A total of 76,668 [45,990 (60%) RSV A and 30,678 (40%) RSV B] positive samples from 83 countries were identified and included in the analysis. Genotype assignment was obtained in 5,340 RSV A and 2,518 RSV B sequences. Two patterns of RSV circulation were observed: continuous seasons with RSV A predominance and alternate predominance of RSV A and B. These patterns were observed in all regions, but the predominant RSV group seldom coincided in all continents during a given year or season. The most frequently identified RSV A genotype was NA1 (including ON1 viruses) (76.30%), and the most frequently identified RSV B genotype was BA (70.65%). Multiple genotypes circulated simultaneously throughout the evolutionary history of RSV, but genotype diversity decreased after the year 2000. The classification of RSV group and genotype is important for the development of vaccines, as well as to understand viral dynamics. This study displays the global and continental RSV circulation patterns from the first report of human RSV infection until the end of 2020.

Respiratory syncytial virus A genotype classification based on systematic intergenotypic and intragenotypic sequence analysis.

Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections, is classified in two major groups (A and B) with multiple genotypes within them. Continuous changes in spatiotemporal distribution of RSV genotypes have been recorded since the identification of this virus. However, there are no established criteria for genotype definition, which affects the understanding of viral evolution, immunity, and development of vaccines. We conducted a phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences, and used 1,103 complete genome sequences to analyze the totallity of RSV-A genes. Intra- and intergenotype p-distance analysis and identification of molecular markers associated to specific genotypes were performed. Our results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1. We propose the analysis of the G gene ectodomain with a wide set of reference sequences of all genotypes for an accurate genotype identification.