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Background Severe acute respiratory infection (SARI) threatens human health and even survival, causing a huge number of hospitalized patients every year. However, as one of the most common respiratory viruses circulated worldwide, the epidemiological and phylogenetic characteristics of human parainfluenza virus (HPIV) in these cases were not well known. Objectives To reveal the epidemiological features of HPIV infection in SARIs in Beijing area from September 2014 to August 2016. Methods A total of 1229 SARI cases in Beijing area were enrolled, investigated, sampled, and tested by multiplex real‐time PCR to identify HPIVs and other common respiratory viruses. Eighteen HPIV‐3 viruses isolated from all HPIV‐positive samples in these SARI cases were sequenced and analyzed. Results Among all enrolled cases, 0.81%, 0.73%, 4.48%, and 0.57% were positive for HPIV‐1 to HPIV‐4, respectively. The highest yield rate of HPIV infection occurred in children under 5 years old (9.07%), followed by the patients over 60 years old (6.02%). The phylogenetic information of HPIV‐3 showed that all viruses belonged to Cluster C3a. Conclusions Besides the young children, the elders older than 60 years also showed a relatively high infection rate of HPIVs, which should be given comparable attentions. Moreover, the HPIV‐3 circulating in China undergoes continued evolution, suggesting the potential risk of evolved HPIV infection should not be overlooked.

Newcastle disease virus (NDV) sub-genotype VII.1.1 is the most common circulating NDV in Iran. In this study, a velogenic NDV isolate was plaque purified and then characterized according to Office International des Epizooties (OIE) standard protocols. The biological properties of the purified isolate named CH/RT40/IR/2011 were characterized using sequencing and phylogenetic analysis, measurement of pathogenicity indexes and challenge studies. The isolate was plaque purified on chicken embryo fibroblast cells for three rounds and then characterized using molecular and biological approaches. Phylogenetic and evolutionary distance analysis of fusion and hemagglutinin-neuraminidase genes classified the virus in sub-genotype VII.1.1. No mutation was observed in the glycosylation and neutralizing epitope sites of the fusion and hemagglutinin-neuraminidase proteins compared to other reported Iranian NDV VII.1.1 isolates. The presence of the 112RRQKRF117 motif in the fusion protein cleavage site together with mean death time, intracerebral pathogenicity index and intravenous pathogenicity index of 57 hr, 1.80 and 2.50 respectively, revealed that the RT40 isolate was a velogenic NDV. In the challenge study, all chickens were inoculated via eye drop, and intranasal route with RT40 isolate died within a week. While all chickens in the vaccinated and challenged group survived and showed no clinical signs. In conclusion, according to genetic analysis, pathotyping and challenge study, the RT40 isolate was similar to virulent NDVs in Iran and was a suitable candidate for a national standard challenge strain, vaccine trials and vaccine production in commercial levers.

The resurgence of mumps in vaccinated adult populations has raised concerns about possible waning vaccine immunity or a potential lack of protection to the circulating strain. A number of individual studies have investigated if there are amino acid variations between the circulating wild-type strains and vaccine strains. In these studies, the HN and F mumps surface glycoproteins have been of interest, because of their role in viral infection, and because the HN protein is the target of neutralizing antibodies. Here, we summarize the single nucleotide variants and their potential effect that have been identified between mumps genotypes in the HN and F proteins.

IntroductionGlucose Regulated Proteins/Binding protein (GRP78/Bip), a representative molecular chaperone, effectively influences and actively participates in the replication processes of many viruses. Little is known, however, about the functional involvement of GRP78 in the replication of Newcastle disease virus (NDV) and the underlying mechanisms.MethodsThe method of this study are to establish protein interactomes between host cell proteins and the NDV Hemagglutinin-neuraminidase (HN) protein, and to systematically investigate the regulatory role of the GRP78-HN protein interaction during the NDV replication cycle.ResultsOur study revealed that GRP78 is upregulated during NDV infection, and its direct interaction with HN is mediated by the N-terminal 326 amino acid region. Knockdown of GRP78 by small interfering RNAs (siRNAs) significantly suppressed NDV infection and replication. Conversely, overexpression of GRP78 resulted in a significant increase in NDV replication, demonstrating its role as a positive regulator in the NDV replication cycle. We further showed that the direct interaction between GRP78 and HN protein enhanced the attachment of NDV to cells, and masking of GRP78 expressed on the cell surface with specific polyclonal antibodies (pAbs) inhibited NDV attachment and replication.DiscussionThese findings highlight the essential role of GRP78 in the adsorption stage during the NDV infection cycle, and, importantly, identify the critical domain required for GRP78-HN interaction, providing novel insights into the molecular mechanisms involved in NDV replication and infection.

Human parainfluenza viruses (HPIVs) are responsible for a wide range of respiratory infections in humans, particularly in children, the elderly, and immunocompromised individuals. This paper presents a study regarding the antiviral activity of a series of 3-phenyl-5-sulfamoyl-N-(7/8/9-(non)substituted-3-oxo-1-thia-4- azaspiro[4.4]non/[4.5]dec-4-yl)-1H-indole-2-carboxamide derivatives against HPIV-2. Our findings suggest the compounds displayed low potency against HPIV-2. Compounds 4 and 8 exhibited the most potent antiviral effects with inhibition of 95.46 and 90.90 % at 10 mg/mL, respectively. Molecular modeling studies were conducted on hemagglutinin-neuraminidase, a crucial druggable target for HPIV, to predict the binding modes of the compounds.

Newcastle disease has been endemic within the Iranian poultry industry for decades. However, the genetic nature of the circulating Hemagglutinin-Neuraminidase (HN) gene among Iranian domesticated bird populations is broadly unexplored. The presented study was carried out to gain insights into the biological and molecular characterization of four complete HN genes isolated from turkey, peacock, and broiler isolates in Iran between 2018 and 2020. The phylogenetic analysis revealed that the isolates belong to the Newcastle disease virus (NDV) subgenotype VII.1.1, previously known as VIIL. Further analysis demonstrated the thermostable substitutions S315P and I369V within the isolates. Finding the N-glycosylation site (NIS) at positions 144–146 and the cysteine residue 123 might influence the fusogenicity abilities of the isolates, while identification of multiple amino acid substitutions in both antigenic sites, especially I514V and E347Q, and the binding sites of the HN protein, raised concern about the pathogenicity of the isolates. In addition, the annual rate of change based on the HN gene of Iranian NDV was calculated at about 1.8088E-3 between 2011 and 2020. In conclusion, a new NDV variant with multiple site mutagenesis is circulating not only among chickens but also in turkey and captive birds such as peafowls, and failure of routine vaccination programs could be attributed to the differences between circulating NDV strains and those used in vaccine manufacturing. Therefore, future legislation aimed at providing vaster vaccination cover and biosecurity plans will be needed to control the spread of circulating NDV strains.

Newcastle disease virus (NDV) genotype VI from pigeon origin is an important causative agent for serious disease in pigeons. Although the biological characteristics of genotype VI NDV have been extensively studied, the understanding of the thermostability of this genotype is still incomplete. In this study, an NDV strain, designated P0506, was isolated from a diseased pigeon in China and classified as genotype VI. Phylogenetic analysis on the basis of the Fusion gene coding sequence indicated that P0506 belonged to sub-genotype VI.2.1.1.2.2 of class II. The thermostability may be a universal characteristic of genotype VI NDV. Thus, the thermostability of two strains, including P0506 identified in this study and P0713 identified previously, belonging to VI.2.1.1.2.2, and another previously isolated strain, P0813, in VI.2.1.1.2.1, was investigated. It was indicated that all three viruses presented resistance to heat treatment, but P0713 was more robust than P0813 and P0506. By constructing a series of HN protein mutants, amino acid residues at both residues 365 and 497 in HN protein were found to be involved in the heat resistance. Furthermore, the effects of residues 365 and 497 in HN protein on the thermostability of the virus were further evaluated by using recombinant viruses generated by the reverse genetic system. Our results showed that residue at position 365 in HN protein was the key thermostable determinant of sub-genotype VI.2.1.1.2.2 NDV. These findings will help us better understand the thermostable mechanism of NDV and serve as a foundation for the further development of novel thermostable vaccines.

A gene delivery system utilizing lentiviral vectors (LVs) requires high transduction efficiency for successful application in human gene therapy. Pseudotyping allows viral tropism to be expanded, widening the usage of LVs. While vesicular stomatitis virus G (VSV-G) single-pseudotyped LVs are commonly used, dual-pseudotyping is less frequently employed because of its increased complexity. In this study, we examined the potential of phenotypically mixed heterologous dual-pseudotyped LVs with VSV-G and Sendai virus hemagglutinin-neuraminidase (SeV-HN) glycoproteins, termed V/HN-LV. Our findings demonstrated the significantly improved transduction efficiency of V/HN-LV in various cell lines of mice, cynomolgus monkeys, and humans compared with LV pseudotyped with VSV-G alone. Notably, V/HN-LV showed higher transduction efficiency in human cells, including hematopoietic stem cells. The efficient incorporation of wild-type SeV-HN into V/HN-LV depended on VSV-G. SeV-HN removed sialic acid from VSV-G, and the desialylation of VSV-G increased V/HN-LV infectivity. Furthermore, V/HN-LV acquired the ability to recognize sialic acid, particularly N-acetylneuraminic acid on the host cell, enhancing LV infectivity. Overall, VSV-G and SeV-HN synergistically improve LV transduction efficiency and broaden its tropism, indicating their potential use in gene delivery.

Human parainfluenza viruses 3 (hPIV3) are important pathogens, responsible for acute respiratory tract diseases, especially in young children. Information on hPIV3 circulation and their diversity pattern in Russia is limited. The aim of this study was to perform a molecular and genetic characterization of hPIV3 circulating in Saint Petersburg, Russia. From October 2017 to September 2023, 14,704 swabs were screened using real-time reverse transcription-PCR. A phylogenetic analysis of the complete hemagglutinin–neuraminidase (HN) gene was performed. Out of 1334 positive hPIV cases, hPIV3 was the most common subtype. Phylogenetic analysis of the studied and previously published HN sequences revealed four distinct genetic clusters, A, B, C, and D, with Cluster D being first delineated in this study. In addition, two newly subdivided genetic lineages, C5a and C5b, were documented. Phylogenetic analysis revealed that the analyzed Russian strains grouped into Cluster C and D; further subclusters C5a, C5b, C3b, C3e, and C3a. While three strains were classified within cluster D, the majority of isolates fell within subcluster C3a, followed by C5b. Taken together, these findings demonstrate the co-circulation of hPIV3 strains during the study period. This is the first study that describes the genetic and molecular aspects of hPIV3 circulating in Russia. Moreover, our results provide an up-to-date hPIV3 phylogenetic analysis.

Human Parainfluenza Virus (HPIV) Type-1, which is an anti-sense ribonucleic acid (RNA) virus belonging to the paramyxoviridae family, induces upper and lower respiratory tract infections. The infections caused by the HPIV Type-1 virus are usually confined to northwestern regions of America. HPIV-1 causes infections through the virulence of the hemagglutinin-neuraminidase (HN) protein, which plays a key role in the attachment of the viral particle with the host’s receptor cells. To the best of our knowledge, there is no effective antiviral drugs or vaccines being developed to combat the infection caused by HPIV-1. In the current study, a multiple epitope-based vaccine was designed against HPIV-1 by taking the viral HN protein as a probable vaccine candidate. The multiple epitopes were selected in accordance with their allergenicity, antigenicity and toxicity scoring. The determined epitopes of the HN protein were connected simultaneously using specific conjugates along with an adjuvant to construct the subunit vaccine, with an antigenicity score of 0.6406. The constructed vaccine model was docked with various Toll-like Receptors (TLRs) and was computationally cloned in a pET28a (+) vector to analyze the expression of vaccine sequence in the biological system. Immune stimulations carried out by the C-ImmSim Server showed an excellent result of the body’s defense system against the constructed vaccine model. The AllerTop tool predicted that the construct was non-allergen with and without the adjuvant sequence, and the VaxiJen 2.0 with 0.4 threshold predicted that the construct was antigenic, while the Toxinpred predicted that the construct was non-toxic. Protparam results showed that the selected protein was stable with 36.48 instability index (II) scores. The Grand average of Hydropathicity or GRAVY score indicated that the constructed protein was hydrophilic in nature. Aliphatic index values (93.53) confirmed that the construct was thermostable. This integrated computational approach shows that the constructed vaccine model has a potential to combat laryngotracheobronchitis infections caused by HPIV-I.