scholarly journals The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 837 ◽  
Author(s):  
Gonzalo Izaguirre

A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity. Surface proteins of enveloped, as well as non-enveloped, viruses become processed by these proteases intracellularly during morphogenesis or extracellularly after egress and during entry in order to produce mature virions activated for infection. Although viruses also take advantage of other proteases, it is when some viruses become reactive with PCs that they may develop high pathogenicity. Besides reacting with furin, some viruses may also react with the PCs of the other specificity group constituted by PC4/PC5/PACE4/PC7. The targeting of PCs for inhibition may result in a useful strategy to treat infections with some highly pathogenic viruses. A wide variety of PC inhibitors have been developed and tested for their antiviral activity in cell-based assays.

2018 ◽  
Vol 28 (34) ◽  
pp. 1800960 ◽  
Author(s):  
Hyun-Ouk Kim ◽  
Woonsung Na ◽  
Minjoo Yeom ◽  
Jihye Choi ◽  
Jihye Kim ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1320
Author(s):  
Yogesh B Narkhede ◽  
Karen J Gonzalez ◽  
Eva-Maria Strauch

The emergence of novel viral infections of zoonotic origin and mutations of existing human pathogenic viruses represent a serious concern for public health. It warrants the establishment of better interventions and protective therapies to combat the virus and prevent its spread. Surface glycoproteins catalyzing the fusion of viral particles and host cells have proven to be an excellent target for antivirals as well as vaccines. This review focuses on recent advances for computational structure-based design of antivirals and vaccines targeting viral fusion machinery to control seasonal and emerging respiratory viruses.


Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Jordana Muñoz-Basagoiti ◽  
Daniel Perez-Zsolt ◽  
Jorge Carrillo ◽  
Julià Blanco ◽  
Bonaventura Clotet ◽  
...  

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.


Cell ◽  
2021 ◽  
Vol 184 (6) ◽  
pp. 1604-1620
Author(s):  
Lu Lu ◽  
Shan Su ◽  
Haitao Yang ◽  
Shibo Jiang

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Kohl ◽  
Annika Brinkmann ◽  
Aleksandar Radonić ◽  
Piotr Wojtek Dabrowski ◽  
Kristin Mühldorfer ◽  
...  

AbstractBats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.


1999 ◽  
Vol 73 (10) ◽  
pp. 8476-8484 ◽  
Author(s):  
Jolanda M. Smit ◽  
Robert Bittman ◽  
Jan Wilschut

ABSTRACT There is controversy as to whether the cell entry mechanism of Sindbis virus (SIN) involves direct fusion of the viral envelope with the plasma membrane at neutral pH or uptake by receptor-mediated endocytosis and subsequent low-pH-induced fusion from within acidic endosomes. Here, we studied the membrane fusion activity of SIN in a liposomal model system. Fusion was followed fluorometrically by monitoring the dilution of pyrene-labeled lipids from biosynthetically labeled virus into unlabeled liposomes or from labeled liposomes into unlabeled virus. Fusion was also assessed on the basis of degradation of the viral core protein by trypsin encapsulated in the liposomes. SIN fused efficiently with receptor-free liposomes, consisting of phospholipids and cholesterol, indicating that receptor interaction is not a mechanistic requirement for fusion of the virus. Fusion was optimal at pH 5.0, with a threshold at pH 6.0, and undetectable at neutral pH, supporting a cell entry mechanism of SIN involving fusion from within acidic endosomes. Under optimal conditions, 60 to 85% of the virus fused, depending on the assay used, corresponding to all of the virus bound to the liposomes as assessed in a direct binding assay. Preincubation of the virus alone at pH 5.0 resulted in a rapid loss of fusion capacity. Fusion of SIN required the presence of both cholesterol and sphingolipid in the target liposomes, cholesterol being primarily involved in low-pH-induced virus-liposome binding and the sphingolipid catalyzing the fusion process itself. Under low-pH conditions, the E2/E1 heterodimeric envelope glycoprotein of the virus dissociated, with formation of a trypsin-resistant E1 homotrimer, which kinetically preceded the fusion reaction, thus suggesting that the E1 trimer represents the fusion-active conformation of the viral spike.


2018 ◽  
Vol 7 (3.1) ◽  
pp. 150
Author(s):  
Sunil Patil ◽  
Chhanwal I.L

Poultry plays a significant role in the Indian economy. Around 60 billion chickens are raised per annum as a basis of food for both their eggs and meat. Poultry meat is in significant source of minerals, protein and various vitamins to balance the diet of human. Broiler farming is an important source of family income depending on size of the farm. Chicken farming in Commercial way is the most fruitful business in India and all around the world. Proper farm management practice and care of birds will result in decent profit in a short span of time. In this paper, we are discussing various diseases caused to poultry hen and their preventing or treating methods. Our results shows that some of disease cannot be cured and only it can be prevented. Spreading of disease with the help of contaminated equipment and infected poultry trade is measured as foremost means of spreading of poultry disease. In some countries migratory birds have also been foremost means of spreading of poultry disease like highly pathogenic viruses. 


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