scholarly journals Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells

2021 ◽  
Vol 17 (9) ◽  
pp. e1009908
Author(s):  
Yuki Kurebayashi ◽  
Shringkhala Bajimaya ◽  
Masahiro Watanabe ◽  
Nicholas Lim ◽  
Michael Lutz ◽  
...  
Keyword(s):  
Virus Type ◽  
Cholesterol Biosynthesis ◽  
Parainfluenza Virus ◽  
Type I ◽  
Human Airway ◽  
Virion Release ◽  
Infected Cells ◽  
Human Parainfluenza Virus ◽  
Airway Cells

Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.

scholarly journals The Long Noncoding Region of the Human Parainfluenza Virus Type 1 F Gene Contributes to the Read-Through Transcription at the M-F Gene Junction

2002 ◽  
Vol 76 (16) ◽  
pp. 8244-8251 ◽  
Author(s):  
Tatiana Bousse ◽  
Tatyana Matrosovich ◽  
Allen Portner ◽  
Atsushi Kato ◽  
Yoshiyuki Nagai ◽  
...  
Keyword(s):  
Virus Type ◽  
Parainfluenza Virus ◽  
Noncoding Sequence ◽  
Wild Type ◽  
F Gene ◽  
Transcriptional Termination ◽  
Infected Cells ◽  
Human Parainfluenza Virus ◽  
Gene Junction

ABSTRACT Sendai virus (SV) and human parainfluenza virus type 1 (hPIV1) have genomes consisting of nonsegmented negative-sense RNA in which the six genes are separated by well-conserved intergenic (IG) sequences and transcriptional start (S) and end signals. In hPIV1-infected cells, transcriptional termination at the M-F gene junction is ineffective; a large number of M-F read-through transcripts are produced (T. Bousse, T. Takimoto, K. G. Murti, and A. Portner, Virology 232:44-52, 1997). In contrast, few M-F read-through transcripts are detected in SV-infected cells. Sequence analysis indicated that the hPIV1 IG and S sequences in the M-F junction differ from those of SV. Furthermore, the hPIV1 F gene contains an unusually long noncoding sequence. To identify the cis-acting elements that prevent transcriptional termination at the M-F junction, we rescued recombinant SV (rSVhMFjCG) in which its M-F gene junction was replaced by that of hPIV1. Cells infected with rSVhMFjCG produced an abundance of M-F read-through transcripts; this result indicated that the hPIV1 M-F junction is responsible for inefficient termination. When one or both of the IG and S sites in rSVhMFjCG were replaced by those of SV, the efficiency of transcriptional termination increased but not to the level observed in wild-type SV-infected cells. Deletion of most of the long noncoding region of the hPIV1 F gene in rSVhMFjCG in addition to the mutations in IG and S signals resulted in efficient termination that was equivalent to the level observed in wild-type virus-infected cells. Therefore, the long noncoding sequence of the hPIV1 F gene contains cis-acting element(s) that affects transcriptional termination. Our evaluation of the effect of inefficient transcriptional termination on viral replication in culture revealed that cells infected with rSVhMFjCG produced less F protein than cells infected with wild-type SV and that assembly of the recombinant SV in culture was less efficient. These phenotypes seem to be responsible for the extended survival of mice infected with rSVhMFjCG.

scholarly journals A study of genetic variability of human parainfluenza virus type 1 in Croatia, 2011–2014

2016 ◽  
Vol 65 (8) ◽  
pp. 793-803 ◽  
Author(s):  
Tanja Košutić-Gulija ◽  
Anamarija Slovic ◽  
Sunčanica Ljubin-Sternak ◽  
Gordana Mlinarić-Galinović ◽  
Dubravko Forčić
Keyword(s):  
Genetic Variability ◽  
Virus Type ◽  
Parainfluenza Virus ◽  
Human Parainfluenza Virus

scholarly journals A novel human parainfluenza virus type 1 (HPIV1) with separated P and C genes is useful for generating C gene mutants for evaluation as live-attenuated virus vaccine candidates

Vaccine ◽  
2010 ◽  
Vol 28 (3) ◽  
pp. 767-779 ◽  
Author(s):  
Emmalene J. Bartlett ◽  
Ann-Marie Cruz ◽  
Jim Boonyaratanakornkit ◽  
Janice Esker ◽  
Adam Castaño ◽  
...  
Keyword(s):  
Virus Type ◽  
Virus Vaccine ◽  
Parainfluenza Virus ◽  
Vaccine Candidates ◽  
Attenuated Virus ◽  
Human Parainfluenza Virus

scholarly journals Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes

2007 ◽  
Vol 4 (1) ◽  
pp. 67 ◽  
Author(s):  
Emmalene J Bartlett ◽  
Adam Castaño ◽  
Sonja R Surman ◽  
Peter L Collins ◽  
Mario H Skiadopoulos ◽  
...  
Keyword(s):  
Virus Type ◽  
Parainfluenza Virus ◽  
Vaccine Candidates ◽  
Human Parainfluenza Virus

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 Transcription by Chemical Cyclin-Dependent Kinase Inhibitors

2001 ◽  
Vol 75 (16) ◽  
pp. 7266-7279 ◽  
Author(s):  
Dai Wang ◽  
Cynthia de la Fuente ◽  
Longwen Deng ◽  
Lai Wang ◽  
Irene Zilberman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Mononuclear Cells ◽  
Virion Release ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
P21 Waf1 ◽  
Hiv 1

ABSTRACT Cyclin-dependent kinases (cdk's) have recently been suggested to regulate human immunodeficiency virus type 1 (HIV-1) transcription. Previously, we have shown that expression of one cdk inhibitor, p21/Waf1, is abrogated in HIV-1 latently infected cells. Based on this result, we investigated the transcription of HIV-1 in the presence of chemical drugs that specifically inhibited cdk activity and functionally mimicked p21/Waf1 activity. HIV-1 production in virally integrated lymphocytic and monocytic cell lines, such as ACH2, 8E5, and U1, as well as activated peripheral blood mononuclear cells infected with syncytium-inducing (SI) or non-syncytium-inducing (NSI) HIV-1 strains, were all inhibited by Roscovitine, a purine derivative that reversibly competes for the ATP binding site present in cdk's. The decrease in viral progeny in the HIV-1-infected cells was correlated with a decrease in the transcription of HIV-1 RNAs in cells treated with Roscovitine and not with the non-cdk general cell cycle inhibitors, such as hydroxyurea (G1/S blocker) or nocodazole (M-phase blocker). Cyclin A- and E-associated histone H1 kinases, as well as cdk 7 and 9 activities, were all inhibited in the presence of Roscovitine. The 50% inhibitory concentration of Roscovitine on cdk's 9 and 7 was determined to be ∼0.6 μM. Roscovitine could selectively sensitize HIV-1-infected cells to apoptosis at concentrations that did not impede the growth and proliferation of uninfected cells. Apoptosis induced by Roscovitine was found in both latent and activated infected cells, as evident by Annexin V staining and the cleavage of the PARP protein by caspase-3. More importantly, contrary to many apoptosis-inducing agents, where the apoptosis of HIV-1-infected cells accompanies production and release of infectious HIV-1 viral particles, Roscovitine treatment selectively killed HIV-1-infected cells without virion release. Collectively, our data suggest that cdk's are required for efficient HIV-1 transcription and, therefore, we propose specific cdk inhibitors as potential antiviral agents in the treatment of AIDS.

Viral Cross-Reactivity and Antigenic Determinants Recognized by Human Parainfluenza Virus Type 1-Specific Cytotoxic T-Cells

Virology ◽  
1994 ◽  
Vol 199 (2) ◽  
pp. 376-383 ◽  
Author(s):  
Vibhuti P. Dave ◽  
Jane E. Allan ◽  
Karen S. Slobod ◽  
F.Suzette Smith ◽  
Kevin W. Ryan ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Type ◽  
Cytotoxic T Cells ◽  
Cross Reactivity ◽  
Parainfluenza Virus ◽  
Antigenic Determinants ◽  
Human Parainfluenza Virus

scholarly journals Generation of Recombinant Human Parainfluenza Virus Type 1 Vaccine Candidates by Importation of Temperature-Sensitive and Attenuating Mutations from Heterologous Paramyxoviruses

2004 ◽  
Vol 78 (4) ◽  
pp. 2017-2028 ◽  
Author(s):  
Jason T. Newman ◽  
Jeffrey M. Riggs ◽  
Sonja R. Surman ◽  
Josephine M. McAuliffe ◽  
Teresa A. Mulaikal ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Virus Type ◽  
Neutralizing Antibodies ◽  
Effective Means ◽  
Parainfluenza Virus ◽  
Temperature Sensitive ◽  
C Protein ◽  
Vaccine Candidates ◽  
Human Parainfluenza Virus

ABSTRACT Human parainfluenza virus type 1 (HPIV1) is a significant cause of respiratory tract disease in infants and young children for which a vaccine is needed. In the present study, we sought to attenuate HPIV1 by the importation of one or more known attenuating point mutations from heterologous paramyxoviruses into homologous sites in HPIV1. The introduced mutations were derived from three attenuated paramyxoviruses: (i) HPIV3cp45, a live-attenuated HPIV3 vaccine candidate containing multiple attenuating mutations; (ii) the respiratory syncytial virus cpts530 with an attenuating mutation in the L polymerase protein; and (iii) a murine PIV1 (MPIV1) attenuated by a mutation in the accessory C protein. Recombinant HPIV1 (rHPIV1) mutants bearing a single imported mutation in C, any of three different mutations in L, or a pair of mutations in F exhibited a 100-fold or greater reduction in replication in the upper or lower respiratory tract of hamsters. Both temperature-sensitive (ts) (mutations in the L and F proteins) and non-ts (the mutation in the C protein) attenuating mutations were identified. rHPIV1 mutants containing a combination of mutations in L were generated that were more attenuated than viruses bearing the individual mutations, showing that the systematic accretion of mutations can yield progressive increases in attenuation. Hamsters immunized with rHPIV1 mutants bearing one or two mutations developed neutralizing antibodies and were resistant to challenge with wild-type HPIV1. Thus, importation of attenuating mutations from heterologous viruses is an effective means for rapidly identifying mutations that attenuate HPIV1 and for generating live-attenuated HPIV1 vaccine candidates.

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