parainfluenza virus
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Author(s):  
L. V. Butakova ◽  
E. Yu. Sapega ◽  
O. E. Trotsenko ◽  
L. A. Balakhontseva ◽  
E. N. Prisyazhnyuk ◽  
...  

Introduction. Emergence and spread of new coronavirus SARS-CoV-2 among population of the Khabarovsk krai influenced the growth of reported cases of community-acquired pneumonia in year 2020. Aim. To determine proportion of other respiratory viruses in development of viral pneumonia epidemic process in the Khabarovsk city in year 2020 during COVID-19 pandemic. Materials and methods. Sputum of 346 patients with community-acquired pneumonia that were hospitalized with suspected diagnosis of COVID-19 was analyzed during year 2020 in Khabarovsk city. Identification of viral agents was performed via real-time reverse-transcriptase polymerase chain reaction. Results. SARSCOV-2 RNA was identified in 183 (52.9%) out of 346 patients. Among other respiratory viruses parainfluenza virus type 3 and rhinoviruses were dominant mostly in SARS-CoV-2 negative examined people. It should be noted that etiology of pneumonia was identified only in 12.9% of all cases in this group (163 people). Co-infection with SARS-CoV-2 and other respiratory viruses such as parainfluenza virus type 3 virus, other coronaviruses and adenovirus was detected only in 2.2% of the cases. Conclusion. Low level of respiratory viruses detection in sputum can be caused by poor technique of sample collection in the hospital, disruption of storage and transportation conditions as well as development of secondary bacterial infection in certain patients. In order to evaluate influence of other respiratory viruses on the course of COVID-19 with underlying coinfection further investigation including analysis of patients’ clinical data is needed.


2021 ◽  
Author(s):  
Naoki Saka ◽  
Yusuke Matsumoto ◽  
Keisuke Ohta ◽  
Daniel Kolakofsky ◽  
Machiko Nishio

Paramyxovirus genomes, like that of human parainfluenza virus type 2 (hPIV2), are precisely a multiple of six nucleotides long (“rule of six”), in which each nucleoprotein subunit (NP) binds precisely 6 nucleotides. Ten residues of its RNA binding groove contact the genome RNA; but only one, Q202, directly contacts a nucleotide base. Mutation of NP Q202 leads to two phenotypes; the ability of the viral polymerase to replicate minigenomes with defective bipartite promoters where NP wt is inactive, and the inability to rescue rPIV2 carrying this point mutation by standard means. The absence a rPIV2 NP Q202A prevented further study of this latter phenotype. By extensive and repeated co-cultivation of transfected cells, a rPIV2 carrying this mutation was finally recovered, and this virus was apparently viable due to the presence of an additional NP mutation (I35L). Our results suggest that these two phenotypes are due to separate effects of the Q202 mutation, and that of the problematic rescue phenotype may be due to the inability of the transfected cell to incorporate viral nucleocapsids during virus budding. Importance Paramyxovirus genomes are contained within a non-covalent homopolymer of its nucleoprotein (NP) and form helical nucleocapsids (NC) whose 3’ ends contain the promoters for the initiation of viral RNA synthesis. This work suggests that these NC 3’ ends may play another role in the virus life cycle, namely via their specific interaction with virus modified cell membranes needed for the incorporation of viral NCs into budding virions.


2021 ◽  
Vol 118 (50) ◽  
pp. e2109744118
Author(s):  
Xueqiao Liu ◽  
Cindy Luongo ◽  
Yumiko Matsuoka ◽  
Hong-Su Park ◽  
Celia Santos ◽  
...  

Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2–neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 107 TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P–immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jade Lee Lee Teng ◽  
Ulrich Wernery ◽  
Hwei Huih Lee ◽  
Joshua Fung ◽  
Sunitha Joseph ◽  
...  

Since the emergence of Middle East Respiratory Syndrome (MERS) in 2012, there have been a surge in the discovery and evolutionary studies of viruses in dromedaries. Here, we investigated a herd of nine dromedary calves from Umm Al Quwain, the United Arab Emirates that developed respiratory signs. Viral culture of the nasal swabs from the nine calves on Vero cells showed two different types of cytopathic effects (CPEs), suggesting the presence of two different viruses. Three samples showed typical CPEs of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in Vero cells, which was confirmed by partial RdRp gene sequencing. Complete genome sequencing of the three MERS-CoV strains showed that they belonged to clade B3, most closely related to another dromedary MERS-CoV isolate previously detected in Dubai. They also showed evidence of recombination between lineages B4 and B5 in ORF1ab. Another three samples showed non-typical CPEs of MERS-CoV with cell rounding, progressive degeneration, and detachment. Electron microscopy revealed spherical viral particles with peplomers and diameter of about 170nm. High-throughput sequencing and metagenomic analysis showed that the genome organization (3'-N-P-M-F-HN-L-5') was typical of paramyxovirus. They possessed typical genome features similar to other viruses of the genus Respirovirus, including a conserved motif 323FAPGNYALSYAM336 in the N protein, RNA editing sites 5'-717AAAAAAGGG725-3', and 5'-1038AGAAGAAAGAAAGG1051-3' (mRNA sense) in the P gene with multiple polypeptides coding capacity, a nuclear localization signal sequence 245KVGRMYSVEYCKQKIEK261 in the M protein, a conserved sialic acid binding motif 252NRKSCS257 in the HN protein, conserved lengths of the leader (55nt) and trailer (51nt) sequences, total coding percentages (92.6–93.4%), gene-start (AGGANNAAAG), gene-end (NANNANNAAAAA), and trinucleotide intergenic sequences (CTT, mRNA sense). Phylogenetic analysis of their complete genomes showed that they were most closely related to bovine parainfluenza virus 3 (PIV3) genotype C strains. In the phylogenetic tree constructed using the complete L protein, the branch length between dromedary camel PIV3 (DcPIV3) and the nearest node is 0.04, which is >0.03, the definition used for species demarcation in the family Paramyxoviridae. Therefore, we show that DcPIV3 is a novel species of the genus Respirovirus that co-circulated with MERS-CoV in a dromedary herd in the Middle East.


2021 ◽  
Author(s):  
Xiaofei Dong ◽  
Xue Wang ◽  
Mengjia Xie ◽  
Wei Wu ◽  
Zhongzhou Chen

Human parainfluenza virus 3 (HPIV3) belongs to the Paramyxoviridae , causing annual worldwide epidemics of respiratory diseases, especially in newborns and infants. The core components consist of just three viral proteins: nucleoprotein (N), phosphoprotein (P), and RNA polymerase (L), playing essential roles in replication and transcription of HPIV3 as well as other paramyxoviruses. Viral genome encapsidated by N is as a template and recognized by RNA-dependent RNA polymerase complex composed of L and P. The offspring RNA also needs to assemble with N to form nucleocapsids. The N is one of the most abundant viral proteins in infected cells and chaperoned in the RNA-free form (N 0 ) by P before encapsidation. In this study, we presented the structure of unassembled HPIV3 N 0 in complex with the N-terminal portion of the P, revealing the molecular details of the N 0 and the conserved N 0 -P interaction. Combined with biological experiments, we showed that the P binds to the C-terminal domain of N 0 mainly by hydrophobic interaction and maintains the unassembled conformation of N by interfering with the formation of N-RNA oligomers, which might be a target for drug development. Based on the complex structure, we developed a method to obtain the monomeric N 0 . Furthermore, we designed a P-derived fusion peptide with 10-times higher affinity, which hijacked the N and interfered with the binding of the N to RNA significantly. Finally, we proposed a model of conformational transition of N from the unassembled state to the assembled state, which helped to further understand viral replication. IMPORTANCE Human parainfluenza virus 3 causes annual epidemics of respiratory diseases, especially in newborns and infants. For the replication of HPIV3 and other paramyxoviruses, only three viral proteins are required: phosphoprotein (P), RNA polymerase (L), and nucleoprotein (N). Here, we reported the crystal structure of the complex of N and its chaperone P. We described in details how P acts as a chaperone to maintain the unassembled conformation of N. Our analysis indicated that the interaction between P and N is conserved and mediated by hydrophobicity, which can be used as a target for drug development. We obtained a high-affinity P-derived peptide inhibitor, specifically targeted N and greatly interfered with the binding of the N to RNA, thereby inhibiting viral encapsidation and replication. In summary, our results provide new insights into the paramyxovirus genome replication and nucleocapsid assembly, and lay the basis for drug development.


iScience ◽  
2021 ◽  
pp. 103379
Author(s):  
Junpei Ohtsuka ◽  
Masaki Imai ◽  
Masayuki Fukumura ◽  
Mitsuyo Maeda ◽  
Asami Eguchi ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1603
Author(s):  
Joaquin Rodriguez Galvan ◽  
Brianna Donner ◽  
Cat Hoang Veseley ◽  
Patrick Reardon ◽  
Heather M. Forsythe ◽  
...  

The human parainfluenza virus 3 (HPIV3) poses a risk for pneumonia development in young children and immunocompromised patients. To investigate mechanisms of HPIV3 pathogenesis, we characterized the association state and host protein interactions of HPIV3 phosphoprotein (HPIV3 P), an indispensable viral polymerase cofactor. Sequence analysis and homology modeling predict that HPIV3 P possesses a long, disordered N-terminal tail (PTAIL) a coiled-coil multimerization domain (PMD), similar to the well-characterized paramyxovirus phosphoproteins from measles and Sendai viruses. Using a recombinantly expressed and purified construct of PMD and PTAIL, we show that HPIV3 P in solution is primarily an alpha-helical tetramer that is stable up to 60 °C. Pulldown and isothermal titration calorimetry experiments revealed that HPIV3 P binds the host hub protein LC8, and turbidity experiments demonstrated a new role for LC8 in increasing the solubility of HPIV3 P in the presence of crowding agents such as RNA. For comparison, we show that the multimerization domain of the Zaire Ebola virus phosphoprotein VP35 is also a tetramer and binds LC8 but with significantly higher affinity. Comparative analysis of the domain architecture of various virus phosphoproteins in the order Mononegavirales show multiple predicted and verified LC8 binding motifs, suggesting its prevalence and importance in regulating viral phosphoprotein structures. Our work provides evidence for LC8 binding to phosphoproteins with multiple association states, either tetrameric, as in the HPIV3 and Ebola phosphoproteins shown here, or dimeric as in rabies virus phosphoprotein. Taken together the data suggest that the association states of a virus-specific phosphoprotein and the complex formed by binding of the phosphoprotein to host LC8 are important regulators of viral function.


Author(s):  
Alexander L. Greninger ◽  
Ksenia Rybkina ◽  
Michelle J. Lin ◽  
Jennifer Drew-Bear ◽  
Tara C. Marcink ◽  
...  

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