scholarly journals The 40 kDa Linear Polyethylenimine Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection by Blocking Its Attachment to Permissive Cells

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 876 ◽  
Author(s):  
Jie Wang ◽  
Jie Li ◽  
Nana Wang ◽  
Qi Ji ◽  
Mingshuo Li ◽  
...  

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in pigs worldwide. The causative agent is the PRRS virus (PRRSV). In this study, we explored polyethylenimine (PEI), a cationic polymer with different forms (linear or branched), to inhibit the replication of PRRSV. Our results demonstrate that the linear but not the 40 kDa branched PEI, or the 25 kDa linear PEI, were well tolerated in cultured cells and exhibited a broad-spectrum inhibition of heterogeneous PRRSV-2 isolates in both MARC-145 cells and primary porcine pulmonary alveolar macrophages (PAMs). Further analysis suggests that PEI could prevent the attachment of PRRSV virions to the susceptible cells. Notably, PEI had a minimal effect on PRRSV internalization in MARC-145 cells, whereas PEI promoted the internalization of PRRSV virions in PAMs, which suggests that these two types of cells might have different internalization processes of PRRSV virions. In conclusion, our data demonstrate that PEI could be used as a novel inhibitor against PRRSV.

2009 ◽  
Vol 390 (3) ◽  
Author(s):  
Cheng Song ◽  
Ray Lu ◽  
Dorothee Bienzle ◽  
Hsiao-Ching Liu ◽  
Dongwan Yoo

AbstractPorcine reproductive and respiratory syndrome (PRRS) virus is an RNA virus that replicates in the cytoplasm, but the viral nucleocapsid (N) protein localizes specifically in the nucleus and nucleolus of virus-infected cells. Nuclear localization of N is non-essential for PRRSV replication in cultured cells but has been shown to modulate the pathogenesis of virus in pigs, suggesting that N plays an accessory role in the nucleus during infection. We identified by yeast two-hybrid screening the inhibitor of MyoD family-a (I-mfa) domain-containing protein (HIC) as a cellular partner for PRRS virus (PRRSV) N protein. This protein is a homolog of human HIC, a recently identified cellular transcription factor. The specific interaction of PRRSV N with HIC was confirmed in cells by mammalian two-hybrid assay and co-immunoprecipitation andin vitroby GST pull-down assay. HIC is a zinc-binding protein and confocal microscopy demonstrated co-localization of N with the HIC-p40 isomer in the nucleus and nucleolus, and in the cytoplasm with HIC-p32, which is the N-terminal truncation of HIC-p40. The porcine homolog of HIC is universally expressed in pig tissues including alveolar macrophages. The interaction of viral capsid with the cellular transcription factor implicates a possible regulation of host cell gene expression by the N protein during PRRSV infection.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Hongfang Ma ◽  
Rui Li ◽  
Longguang Jiang ◽  
Songlin Qiao ◽  
Xin-xin Chen ◽  
...  

AbstractPorcine reproductive and respiratory syndrome (PRRS) is a serious disease burdening global swine industry. Infection by its etiological agent, PRRS virus (PRRSV), shows a highly restricted tropism of host cells and has been demonstrated to be mediated by an essential scavenger receptor (SR) CD163. CD163 fifth SR cysteine-rich domain (SRCR5) is further proven to play a crucial role during viral infection. Despite intense research, the involvement of CD163 SRCR5 in PRRSV infection remains to be elucidated. In the current study, we prepared recombinant monkey CD163 (moCD163) SRCR5 and human CD163-like homolog (hCD163L1) SRCR8, and determined their crystal structures. After comparison with the previously reported crystal structure of porcine CD163 (pCD163) SRCR5, these structures showed almost identical structural folds but significantly different surface electrostatic potentials. Based on these differences, we carried out mutational research to identify that the charged residue at position 534 in association with the one at position 561 were important for PRRSV-2 infection in vitro. Altogether the current work sheds some light on CD163-mediated PRRSV-2 infection and deepens our understanding of the viral pathogenesis, which will provide clues for prevention and control of PRRS.


Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 354
Author(s):  
Chia-Ming Su ◽  
Raymond Robert Richard Rowland ◽  
Dongwan Yoo

Cellular receptors play a critical role in viral infection. At least seven cellular molecules have been identified as putative viral entry mediators for porcine reproductive and respiratory syndrome virus (PRRSV). Accumulating data indicate that among these candidates, CD163, a cysteine-rich scavenger receptor on macrophages, is the major receptor for PRRSV. This review discusses the recent advances and understanding of the entry of PRRSV into cells, viral pathogenesis in CD163 gene-edited swine, and CD163 as a potential target of receptor–ligand for the control of PRRS.


The Analyst ◽  
2021 ◽  
Author(s):  
Pengfei Zhang ◽  
Aniruddha Kaushik ◽  
Kathleen E Mach ◽  
Kuangwen Hsieh ◽  
Joseph C. Liao ◽  
...  

The development of accelerated methods for pathogen identification (ID) and antimicrobial susceptibility testing (AST) for infectious diseases is necessary to facilitate evidence-based antibiotic therapy and reduce clinical overreliance on broad-spectrum...


Author(s):  
Polina Trachuk ◽  
Vagish Hemmige ◽  
Ruth Eisenberg ◽  
Kelsie Cowman ◽  
Victor Chen ◽  
...  

Abstract Objective Infection is a leading cause of admission to intensive care units (ICU), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID-Critical Care Medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. Method In this single site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during post-intervention period from January 1, 2017 to December 31, 2017 and compared it to antibiotic utilization in the same ICUs during the pre-intervention period from January 1, 2015 to December 31, 2015. Results Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam and cefepime during the intervention period. When compared to pre-intervention period there was no difference in-hospital mortality, hospital length of stay and re-admission. Conclusion With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.


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