Characterization of Human Parainfluenza Viruses. I. The Structural Proteins of Parainfluenza Virus 2 and their Synthesis in Infected Cells

ABSTRACT Human parainfluenza viruses are important respiratory tract pathogens, especially of children. However, no vaccines or specific therapies for infections caused by these viruses are currently available. In the present study we characterized the efficacy of the novel parainfluenza virus inhibitors BCX 2798 and BCX 2855, which were designed based on the three-dimensional structure of the hemagglutinin-neuraminidase (HN) protein. The compounds were highly effective in inhibiting hemagglutinin (HA) and neuraminidase (NA) activities and the growth of hPIV-1, hPIV-2, and hPIV-3 in LLC-MK2 cells. The concentrations required to reduce the activity to 50% of that of a control ranged from 0.1 to 6.0 μM in HA inhibition assays and from 0.02 to 20 μM in NA inhibition assays. The concentrations required to inhibit virus replication to 50% of the level of the control ranged from 0.7 to 11.5 μM. BCX 2798 and BCX 2855 were inactive against influenza virus HA and NA and bacterial NA. In mice infected with a recombinant Sendai virus whose HN gene was replaced with that of hPIV-1 [rSV(hHN)], intranasal administration of BCX 2798 (10 mg/kg per day) and of BCX 2855 (50 mg/kg per day) 4 h before the start of infection resulted in a significant reduction in titers of virus in the lungs and protection from death. Treatment beginning 24 h after the start of infection did not prevent death. Together, our results indicate that BCX 2798 and BCX 2855 are effective inhibitors of parainfluenza virus HN and may limit parainfluenza virus infections in humans.

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Virological Surveillance and Molecular Characterization of Human Parainfluenzavirus Infection in Children with Acute Respiratory Illness: Germany, 2015–2019

Microorganisms ◽

10.3390/microorganisms9071508 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1508

Author(s):

Djin-Ye Oh ◽

Barbara Biere ◽

Markus Grenz ◽

Thorsten Wolff ◽

Brunhilde Schweiger ◽

...

Keyword(s):

Young Children ◽

Respiratory Infections ◽

National Level ◽

Respiratory Illness ◽

Phylogenetic Characterization ◽

Parainfluenza Viruses ◽

Human Parainfluenza Viruses ◽

Respiratory Specimens ◽

Virological Surveillance

Human parainfluenza viruses (HPIVs) are important causes of respiratory illness, especially in young children. However, surveillance for HPIV is rarely performed continuously, and national-level epidemiologic and genetic data are scarce. Within the German sentinel system, to monitor acute respiratory infections (ARI), 4463 respiratory specimens collected from outpatients <5 years of age between October 2015 and September 2019 were retrospectively screened for HPIV 1–4 using real-time PCR. HPIV was identified in 459 (10%) samples. HPIV-3 was the most common HPIV-type, with 234 detections, followed by HPIV-1 (113), HPIV-4 (61), and HPIV-2 (49). HPIV-3 was more frequently associated with age <2 years, and HPIV-4 was more frequently associated with pneumonia compared to other HPIV types. HPIV circulation displayed distinct seasonal patterns, which appeared to vary by type. Phylogenetic characterization clustered HPIV-1 in Clades 2 and 3. Reclassification was performed for HPIV-2, provisionally assigning two distinct HPIV-2 groups and six clades, with German HPIV-2s clustering in Clade 2.4. HPIV-3 clustered in C1, C3, C5, and, interestingly, in A. HPIV-4 clustered in Clades 2.1 and 2.2. The results of this study may serve to inform future approaches to diagnose and prevent HPIV infections, which contribute substantially to ARI in young children in Germany.

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Complete Genome Characterization of Eight Human Parainfluenza Viruses from the Netherlands

Microbiology Resource Announcements ◽

10.1128/mra.00125-19 ◽

2019 ◽

Vol 8 (15) ◽

Author(s):

My V. T. Phan ◽

Georgina Arron ◽

Corine H. GeurtsvanKessel ◽

Robin C. Huisman ◽

Richard Molenkamp ◽

...

Keyword(s):

The Netherlands ◽

Complete Genome ◽

Full Genome ◽

Genome Sequences ◽

Content Type ◽

Genome Characterization ◽

Parainfluenza Viruses ◽

Human Parainfluenza Viruses ◽

Generation Sequencing

We report the complete genome sequences of eight human parainfluenza viruses (HPIV) belonging to Human respirovirus 1 (HPIV-1), Human respirovirus 3 (HPIV-3), Human rubulavirus 2 (HPIV-2), and Human rubulavirus 4 (HPIV-4). The genome sequences were generated using random-primed next-generation sequencing and represent the first HPIV full-genome sequences from the Netherlands.

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Characterization of human parainfluenza virus 3 recovered from persistently infected cells

Virus Research ◽

10.1016/0168-1702(88)90189-x ◽

1988 ◽

Vol 11 ◽

pp. 49

Author(s):

Donald G. Murphy ◽

Kenneth Dimock ◽

C.Yong Kang

Keyword(s):

Parainfluenza Virus ◽

Persistently Infected ◽

Infected Cells ◽

Human Parainfluenza Virus

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Characterization of human parainfluenza virus type 2 RNAs in infected cells and by in vitro synthesis

Virus Research ◽

10.1016/0168-1702(94)00095-t ◽

1995 ◽

Vol 35 (2) ◽

pp. 181-192

Author(s):

Yung T. Huang ◽

Rita R. Romito ◽

Milita Panin

Keyword(s):

Virus Type ◽

Parainfluenza Virus ◽

In Vitro Synthesis ◽

Infected Cells ◽

Human Parainfluenza Virus

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The Viral Polymerase Complex Mediates the Interaction of vRNPs with Recycling Endosomes During SeV Assembly

10.1101/2020.04.23.058883 ◽

2020 ◽

Author(s):

Emmanuelle Genoyer ◽

Katarzyna Kulej ◽

Chuan Tien Hung ◽

Patricia A. Thibault ◽

Kristopher Azarm ◽

...

Keyword(s):

Sendai Virus ◽

Initial Step ◽

Viral Proteins ◽

Viral Polymerase ◽

Recycling Endosomes ◽

Viral Genomes ◽

Parainfluenza Viruses ◽

Infected Cells ◽

Human Parainfluenza Viruses

ABSTRACTParamyxoviruses are negative sense single-stranded RNA viruses that comprise many important human and animal pathogens, including human parainfluenza viruses. These viruses bud from the plasma membrane of infected cells after the viral ribonucleoprotein complex (vRNP) is transported from the cytoplasm to the cell membrane via Rab11a-marked recycling endosomes. The viral proteins that are critical for mediating this important initial step in viral assembly are unknown. Here we use the model paramyxovirus, murine parainfluenza virus 1, or Sendai virus (SeV), to investigate the roles of viral proteins in Rab11a-driven virion assembly. We previously reported that infection with SeV containing high levels of copy-back defective viral genomes (DVGs) generates heterogenous populations of cells. Cells enriched in full-length virus produce viral particles containing standard or defective viral genomes, while cells enriched in DVGs do not, despite high levels of defective viral genome replication. Here we take advantage of this heterogenous cell phenotype to identify proteins that mediate interaction of vRNPs with Rab11a. We examine the role of matrix protein and nucleoprotein and determine that they are not sufficient to drive interaction of vRNPs with recycling endosomes. Using a combination of mass spectrometry and comparative protein abundance and localization in DVG- and FL-high cells, we identify viral polymerase complex components L and, specifically, its cofactor C proteins as interactors with Rab11a. We find that accumulation of these proteins within the cell is the defining feature that differentiates cells that proceed to viral egress from cells which remain in replication phases.IMPORTANCEParamyxoviruses are a family of viruses that include a number of pathogens with significant burdens on human health. Particularly, human parainfluenza viruses are an important cause of pneumonia and bronchiolitis in children for which there are no vaccines or direct acting antivirals. These cytoplasmic replicating viruses bud from the plasma membrane and coopt cellular endosomal recycling pathways to traffic viral ribonucleoprotein complexes from the cytoplasm to the membrane of infected cells. The viral proteins required for viral engagement with the recycling endosome pathway are still not known. Here we use the model paramyxovirus Sendai virus, or murine parainfluenza virus 1, to investigate the role of viral proteins in this initial step of viral assembly. We find that viral polymerase components large protein L and accessory C proteins are necessary for engagement with recycling endosomes. These findings are important in identifying viral proteins as potential targets for development of antivirals.

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