Dataset Information

A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3.

ABSTRACT:

Background

Sepsis is a systemic inflammatory response syndrome caused by severe infection in children, but cases of sepsis associated with human parainfluenza virus (HPIV) have been rarely reported in newborns.

Case presentation

We report a case of HPIV-3 positive full-term newborn admitted to the Neonatal Intensive Care Unit of Beijing Children's Hospital due to hematuria, gloomy spirit, inactivity and loss of appetite for 6 h. He had septic shock when he arrived the Accident & Emergency Department requiring immediate intubation and mechanical ventilation. Intravenous antibiotics were started. He had completely negative response to all anti-shock treatments including fluid resuscitation and vasopressor supports, and died 14 h later. Viral nucleic acid detection and metagenomic next-generation sequencing (mNGS) analyses of nasopharyngeal aspirate and blood specimens verified an HPIV-3 infection, with negative bacterial culture results. The HPIV-3 strain detected in this patient was subtyped as HPIV C3a, and two unreported amino acid mutations were found in the HN protein region.

Conclusion

The patient had a severe infection associated with HPIV-3, which was the cause of sepsis and septic shock. This study showed the diagnostic value of mNGS in etiological diagnosis, especially in severe neonatal case.

SUBMITTER: Chen X

PROVIDER: S-EPMC10612315 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3.

Chen Xiangpeng X Wang Hong H Li Qi Q Qi Yujie Y Li Fei F He Wenwen W Wang Qiushi Q Jin Fei F Guo Yanqing Y Hei Mingyan M Xie Zhengde Z

Virology journal 20231027 1

<h4>Background</h4>Sepsis is a systemic inflammatory response syndrome caused by severe infection in children, but cases of sepsis associated with human parainfluenza virus (HPIV) have been rarely reported in newborns.<h4>Case presentation</h4>We report a case of HPIV-3 positive full-term newborn admitted to the Neonatal Intensive Care Unit of Beijing Children's Hospital due to hematuria, gloomy spirit, inactivity and loss of appetite for 6 h. He had septic shock when he arrived the Accident & E ...[more]

PMID: 37891594

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Project description:Viral inclusion bodies (IBs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication. Furthermore, we found that acetylated α-tubulin interacts with the N-P complex and colocalizes with IBs of HPIV3 but does not interact with the N-P complex of human respiratory syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of human respiratory syncytial virus. Most importantly, enhancement of α-tubulin acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), or expression of α-tubulin acetyltransferase 1 (α-TAT1) resulted in the fusion of small IBs into large IBs and effective viral replication. In contrast, suppression of acetylation of α-tubulin by overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and viral replication. Our findings offer previously unidentified mechanistic insights into the regulation of viral IB fusion by acetylated α-tubulin, which is critical for viral replication. Inclusion bodies (IBs) are unique structures generated by viral proteins and some cellular proteins as a platform for efficient viral replication. Human parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower respiratory tract disease in infants and young children. However, no vaccines or antiviral drugs for HPIV3 are available. Therefore, understanding virus-host interactions and developing new antiviral strategies are increasingly important. Acetylation on lysine (K) 40 of α-tubulin is an evolutionarily conserved modification and plays an important role in many cellular processes, but its role in viral IB dynamics has not been fully explored. To our knowledge, our findings are the first to show that acetylated α-tubulin enhances viral replication by regulating HPIV3 IB fusion.

Project description:Human parainfluenza virus type 3 (HPIV3) is a negative-sense single-stranded RNA virus belonging to the Paramyxoviridae family. HPIV3 is a lung-tropic virus causing airway diseases, including pneumonia, croup, and bronchiolitis, during infancy and childhood. The activation of the inflammasome by pathogens results in the production of proinflammatory cytokines such as interleukin-1β (IL-1β) during infection. Thus, the inflammasome-mediated proinflammatory response plays a critical role in regulating the immune response and virus clearance. The inflammasome is a multimeric protein complex triggering caspase-1 activation. Activated caspase-1 cleaves pro-IL-1β into its mature (and active) secretory form. Our study revealed inflammasome activation in macrophages following HPIV3 infection. Specifically, the activation of the NLRP3/ASC inflammasome resulted in the production of mature IL-1β from HPIV3-infected cells. Furthermore, Toll-like receptor 2 (TLR2) activation (first signal) and potassium efflux (second signal) constituted two cellular events mediating inflammasome activation following HPIV3 infection. During our studies, we surprisingly identified the HPIV3 C protein as an antagonist of inflammasome activation. The HPIV3 C protein is an accessory protein encoded by the open reading frame of the viral phosphoprotein (P) gene. The HPIV3 C protein interacted with the NLRP3 protein and blocked inflammasome activation by promoting the proteasomal degradation of the NLRP3 protein. Thus, our studies report NLRP3/ASC inflammasome activation by HPIV3 via TLR2 signaling and potassium efflux. Furthermore, we have identified HPIV3 C as a viral component involved in antagonizing inflammasome activation.IMPORTANCE Human parainfluenza virus type 3 (HPIV3) is a paramyxovirus that causes respiratory tract diseases during infancy and childhood. Currently, there is no effective vaccine or antiviral therapy for HPIV3. Therefore, in order to develop anti-HPIV3 agents (therapeutics and vaccines), it is important to study the HPIV3-host interaction during the immune response. Inflammasomes play an important role in the immune response. Inflammasome activation by HPIV3 has not been previously reported. Our studies demonstrated inflammasome activation by HPIV3 in macrophages. Specifically, HPIV3 activated the NLRP3/ASC inflammasome by TLR2 activation and potassium efflux. C proteins of paramyxoviruses are accessory proteins encoded by the viral phosphoprotein gene. The role of the C protein in inflammasome regulation was unknown. Surprisingly, our studies revealed that the HPIV3 C protein antagonizes inflammasome activation. In addition, we highlighted for the first time a mechanism utilized by paramyxovirus accessory proteins to block inflammasome activation. The HPIV3 C protein interacted with the NLRP3 protein to trigger the proteasomal degradation of the NLRP3 protein.

Dataset Information

A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3.

Background

Case presentation

Conclusion

Publications

A fatal case of neonatal viral sepsis caused by human parainfluenza virus type 3.

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