scholarly journals SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis

Author(s):  
Armin Bayati ◽  
Rahul Kumar ◽  
Vincent Francis ◽  
Peter S. McPherson

AbstractWith more than 51 million cases and 1.3 million deaths, and with the resulting social upheaval, the COVID-19 pandemic presents one of the greatest challenges ever to human society. It is thus vital to fully understand the biology of SARS-CoV-2, the causative agent of COVID-19. SARS-CoV-2 uses its spike glycoprotein to interact with the cell surface as a first step in the infection process. Using purified spike glycoprotein and lentivirus pseudotyped with spike glycoprotein, we now demonstrate that following engagement with the plasma membrane, SARS-CoV-2 undergoes rapid clathrin-mediated endocytosis. This suggests that transfer of viral RNA to the cell cytosol occurs from the lumen of the endosomal system, and importantly clathrin-heavy chain knockdown, which blocks clathrin-mediated endocytosis, reduces viral infectivity. This discovery reveals important new information about the basic biology of SARS-CoV-2 infectivity.

2017 ◽  
Author(s):  
Daniel Benatov

Our conference is the first project of Student Science Association, which was restored in our University in 1998. The main peculiarity of the conference is the student organizing committee. The conference was attended by representatives of Russia, Belarus, Sweden, Poland, Bulgaria, Armenia, Azerbaijan, Czech Republic, Lithuania, Latvia, Georgia, Iran, not mentioning hundreds of Ukrainian participants. We’re happy with the fact that our conference allows students to discover new information, which they wouldn’t find in training courses manuals; contrariwise businesses and organizations can get direct access to young and qualified staff. We believe that events like our conference are useful for the young scientists and also for the public authorities and businesses. Conference "Ecology. Human. Society "is a part of feedback between universities and market participants. The conference has overgrown limits of being simple educational process element. Today, it is a serious recruiting resource for state institutions and businesses - an important part of a mutually beneficial dialogue.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tao Hu ◽  
Zhen Wu ◽  
Shaoxiong Wu ◽  
Shun Chen ◽  
Anchun Cheng

AbstractFlaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.


2020 ◽  
Vol 6 (12) ◽  
pp. eaaz3367 ◽  
Author(s):  
DongXu He ◽  
AiQin Mao ◽  
YouRan Li ◽  
SiuCheung Tam ◽  
YongTang Zheng ◽  
...  

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1–induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1–induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1–infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.


Author(s):  
Pedro Henrique Abreu da Silva ◽  
Andressa Santos Garcia ◽  
Fábio Aguiar Alves ◽  
André Luis Souza dos Santos ◽  
Cátia Lacerda Sodré

: The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in people with diabetes is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1126 ◽  
Author(s):  
Daryl J. V. David ◽  
Pascale Cossart

The bacterial pathogen Listeria monocytogenes (Lm) is the causative agent of listeriosis, a rare but fatal foodborne disease. During infection, Lm can traverse several host barriers and enter the cytosol of a variety of cell types. Thus, consideration of the extracellular and intracellular niches of Lm is critical for understanding the infection process. Here, we review advances in our understanding of Lm infection and highlight how the interactions between the host and the pathogen are context dependent. We discuss discoveries of how Lm senses entry into the host cell cytosol. We present findings concerning how the nature of the various cytoskeleton components subverted by Lm changes depending on both the stage of infection and the subcellular context. We present discoveries of critical components required for Lm traversal of physiological barriers. Interactions between the host gut microbiota and Lm will be briefly discussed. Finally, the importance of Lm biodiversity and post-genomics approaches as a promising way to discover novel virulence factors will be highlighted.


2020 ◽  
Author(s):  
Sean Kennedy ◽  
Mélanie M Leroux ◽  
Alexis Simons ◽  
Brice Malve ◽  
Marc Devocelle ◽  
...  

Human gastroenteritis viruses are amid the major causes of disease worldwide, responsible for more than 2 million deaths per year. Human noroviruses play a leading role in the gastroenteritis outbreaks and the continuous emergence of new strains contributes to the significant morbidity and mortality. Many aspects of the viral entry and infection process remain unclear, including the major response of the host cell to the virus, which is the trigger of several programmed cell death related mechanisms. In this review, we assessed apoptosis and autophagy at various stages in the infection process to provide better understanding of the viral–host interaction. This brings us closer to fully understanding how noroviruses work, thus allowing the development of specific antiviral therapies.


2014 ◽  
Vol 95 (12) ◽  
pp. 2820-2830 ◽  
Author(s):  
Feifei Yin ◽  
Manli Wang ◽  
Ying Tan ◽  
Fei Deng ◽  
Just M. Vlak ◽  
...  

The major envelope fusion protein F of the budded virus of baculoviruses consists of two disulfide-linked subunits: an N-terminal F2 subunit and a C-terminal, membrane-anchored F1 subunit. There is one cysteine in F2 and there are 15 cysteines in F1, but their role in disulfide linking is largely unknown. In this study, the inter- and intra-subunit disulfide bonds of the Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HearNPV) F protein were analysed by site-directed mutagenesis. Results indicated that in a functional F protein, an inter-subunit disulfide bond exists between amino acids C108 (F2) and C241 (F1). When C241 was mutated, an alternative disulfide bond was formed between C108 and C232, rendering F non-functional. No inter-subunit bridge was observed in a double C232/C241 mutant of F1. C403 was not involved in the formation of inter-subunit disulfide bonding, but mutation of this amino acid decreased viral infectivity significantly, suggesting that it might be involved in intra-subunit disulfide bonds. The influence of reductant [tris(2-carboxyethyl) phosphine (TCEP)] and free-thiol inhibitors [4-acetamido-4′-maleimidylstilbene 2,2′-disulfonic acid (AMS) and 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB)] on the infectivity of HearNPV was tested. The results indicated that TCEP greatly decreased the infection of HzAm1 cells by HearNPV. In contrast, AMS and DTNB had no inhibitory effect on viral infectivity. The data suggested that free thiol/disulfide isomerization was not likely to play a role in viral entry and infectivity.


2004 ◽  
Vol 101 (12) ◽  
pp. 4240-4245 ◽  
Author(s):  
G. Simmons ◽  
J. D. Reeves ◽  
A. J. Rennekamp ◽  
S. M. Amberg ◽  
A. J. Piefer ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kuen-Lin Chen ◽  
Zih-Yan Yang ◽  
Chin-Wei Lin

Abstract Background In the past decades, different diseases and viruses, such as Ebola, MERS and COVID-19, impacted the human society and caused huge cost in different fields. With the increasing threat from the new or unknown diseases, the demand of rapid and sensitive assay method is more and more urgent. Results In this work, we developed a magneto-optical biochip based on the Cotton–Mouton effect of γ-Fe2O3@Au core/shell magnetic nanoparticles. We performed a proof-of-concept experiment for the detection of the spike glycoprotein S of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The assay was achieved by measuring the magneto-optical Cotton–Mouton effect of the biochip. This magneto-optical biochip can not only be used to detect SARS-CoV-2 but also can be easily modified for other diseases assay. Conclusion The assay process is simple and the whole testing time takes only 50 min including 3 min for the CM rotation measurement. The detection limit of our method for the spike glycoprotein S of SARS-CoV-2 is estimated as low as 0.27 ng/mL (3.4 pM). Graphic abstract


2021 ◽  
Author(s):  
Diana Schwendener Forkel

In the last twenty years, mathematical modelling (MM) has been notably used to capture the infection kinetics of many infectious diseases as it allows insights into the basic biology, infection kinetics, and the mechanisms and efficacy of treatment modalities. MMs of influenza A virus (IAV) infection usually represent the process of virus replication within a cell as a ‘black box’ term for viral production. The simplification is appropriate when we are not interested in the microscopic details of infection. Recently though, MMs have begun to account for the kinetics of intracellular IAV replication. Herein, we examine the MM by Heldt et al., which is able to capture kinetics of IAV infection. It however, does so by adjusting parameters of the MM to various events in the infection process. We developed a robust, yet concise, MM for the intracellular kinetics of influenza A virus infection in vitro with a consistent set of parameters. We use attachment, fusion and RNA data gathered from literature sources to validate our simplified MM and match known infection kinetics consistent throughout infection.


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