scholarly journals Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2165
Author(s):  
Siobhan Gargan ◽  
Nigel J. Stevenson

The current COVID-19 pandemic has highlighted the need for the research community to develop a better understanding of viruses, in particular their modes of infection and replicative lifecycles, to aid in the development of novel vaccines and much needed anti-viral therapeutics. Several viruses express proteins capable of forming pores in host cellular membranes, termed “Viroporins”. They are a family of small hydrophobic proteins, with at least one amphipathic domain, which characteristically form oligomeric structures with central hydrophilic domains. Consequently, they can facilitate the transport of ions through the hydrophilic core. Viroporins localise to host membranes such as the endoplasmic reticulum and regulate ion homeostasis creating a favourable environment for viral infection. Viroporins also contribute to viral immune evasion via several mechanisms. Given that viroporins are often essential for virion assembly and egress, and as their structural features tend to be evolutionarily conserved, they are attractive targets for anti-viral therapeutics. This review discusses the current knowledge of several viroporins, namely Influenza A virus (IAV) M2, Human Immunodeficiency Virus (HIV)-1 Viral protein U (Vpu), Hepatitis C Virus (HCV) p7, Human Papillomavirus (HPV)-16 E5, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Open Reading Frame (ORF)3a and Polyomavirus agnoprotein. We highlight the intricate but broad immunomodulatory effects of these viroporins and discuss the current antiviral therapies that target them; continually highlighting the need for future investigations to focus on novel therapeutics in the treatment of existing and future emergent viruses.

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 757
Author(s):  
João Diogo Dias ◽  
Nazim Sarica ◽  
Christine Neuveut

Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments efficiently control virus replication and improve liver function, they cannot cure HBV infection. Viral persistence is due to the maintenance of the viral circular episomal DNA, called covalently closed circular DNA (cccDNA), in the nuclei of infected cells. cccDNA not only resists antiviral therapies, but also escapes innate antiviral surveillance. This viral DNA intermediate plays a central role in HBV replication, as cccDNA is the template for the transcription of all viral RNAs, including pregenomic RNA (pgRNA), which in turn feeds the formation of cccDNA through a step of reverse transcription. The establishment and/or expression of cccDNA is thus a prime target for the eradication of HBV. In this review, we provide an update on the current knowledge on the initial steps of HBV infection, from the nuclear import of the nucleocapsid to the formation of the cccDNA.


2003 ◽  
Vol 130 (2) ◽  
pp. 263-271 ◽  
Author(s):  
J. M. L. BROTHERTON ◽  
V. C. DELPECH ◽  
G. L. GILBERT ◽  
S. HATZI ◽  
P. D. PARASKEVOPOULOS ◽  
...  

In September 2000 an outbreak of influenza-like illness was reported on a cruise ship sailing between Sydney and Noumea with over 1100 passengers and 400 crew on board. Laboratory testing of passengers and crew indicated that both influenza A and B had been circulating on the ship. The cruise coincided with the peak influenza period in Sydney. Morbidity was high with 40 passengers hospitalized, two of whom died. A questionnaire was sent to passengers 3 weeks after the cruise and 836 of 1119 (75%) responded. A total of 310 passengers (37%) reported suffering from an influenza-like illness (defined as cough, fever, myalgia and weakness) and 528 (63%) had seen a doctor for illness related to the cruise. One-third of passengers reported receipt of influenza vaccination in 2000; however neither their rates of influenza-like illness nor hospitalization were significantly different from those in unvaccinated passengers. A case–control study also found no significant protective effect of influenza vaccination. With the increasing popularity of cruise vacations, such outbreaks are likely to affect increasing numbers of people. Whilst influenza vaccination of passengers and crew may afford some protection, uptake and effectiveness may not be sufficient to prevent outbreaks. Surveillance systems and early intervention measures, such as antiviral therapies, should be considered to detect and control such outbreaks.


2018 ◽  
Vol 9 ◽  
Author(s):  
Dan Dou ◽  
Rebecca Revol ◽  
Henrik Östbye ◽  
Hao Wang ◽  
Robert Daniels

Pneumologia ◽  
2021 ◽  
Vol 69 (3) ◽  
pp. 151-158
Author(s):  
Raluca Ioana Dospinescu Arcana ◽  
Radu Crișan-Dabija ◽  
Anda Tesloianu ◽  
Daniela Robu Popa ◽  
Oana-Elena Rohozneanu ◽  
...  

Abstract Considering the increased prevalence of influenza infections in the cold season and the pandemic evolution of severe acute respiratory syndrome-CoV-2 (SARS-CoV-2), the medical staffs are facing potential viral co-infection with SARS-CoV-2 and influenza virus. Both viruses belong to the category of ribonucleic acid (RNA) viruses, having common structural features, causing a similar immune response, with a related mode of transmission and with both respiratory and general symptoms. SARS-CoV-2 and influenza viruses cause contagious infections and the protective measures against them are the same: wearing masks in crowded spaces, proper hand hygiene and avoiding crowded places. Co-infections with influenza A and B viruses and SARS-CoV-2 virus involve additional precautions regarding the therapeutic and evolution approach. Studies show that patients who have been vaccinated against influenza have developed milder forms of confirmed SARS-CoV-2 infection. In elderly patients, increased influenza vaccination coverage has shown to be associated with a decrease in mortality rate and also reduced the heavy impact of double infection. The Influenza vaccine can trigger early immune mechanisms in order to facilitate early detection of SARS-CoV-2 as well as its clearance. Influenza vaccination should now be seen, more than ever, as a strategy to combat the growing SARS-CoV-2 pandemic, especially in vulnerable populations (elderly and people with associated comorbidities).


Author(s):  
Perotti M F ◽  
Arce A L ◽  
R L Chan

Abstract Roots are the anchorage organs of plants, responsible for water and nutrient uptake, exhibiting high plasticity. Root architecture is driven by the interactions of biomolecules, including transcription factors (TFs) and hormones that are crucial players regulating root plasticity. Multiple TF families are involved in root development; some, such as ARFs and LBDs, have been well characterized, whereas others remain less investigated. In this review, we synthesize the current knowledge about the involvement of the large family of homeodomain-leucine zipper (HD-Zip) TFs in root development. This family is divided into four subfamilies (I to IV), mainly according to structural features, such as additional motifs aside from HD-Zip, as well as their size, gene structure, and expression patterns. We explored and analyzed public databases and the scientific literature regarding HD-Zip TFs in Arabidopsis and other species. Most members of the four HD-Zip subfamilies are expressed in specific cell types and several ones from each group have assigned functions in root development. Notably, a high proportion of the studied proteins are part of intricate regulation pathways involved in primary and lateral root growth and development.


Author(s):  
Dimitrios Vlachakis ◽  
Argiro Karozou ◽  
Spyridon Champeris Tsaniras ◽  
Sophia Kossida

Currently, humanity lives in the verge of a world-wide epidemic of the H7N9 influenza A virus. This strain has turned out to be very virulent for humans and there have been many reported casualties already in several places around the globe. Concordantly, not much is known for the H7N9 strain. Herein, the authors intend to establish a modest database of current knowledge and informed opinion in different key areas of the H7N9 virus. The source of the virus, its infection routes and mutations remain unclear. Results of several recent studies will be further analyzed including clinical, virological and histopathological manifestations of H7N9, diagnosis modes and viral transmissibility. Treatment, vaccination and public concerns about a pandemic threat will be discussed as well. The present work is expected to act as an updated world reference for the H7N9 influenza A strain. Moreover, modes for tackling H7N9 will be proposed, focusing on RNA polymerase for further investigation as a potential pharmacological target. Hence, invaluable conclusions may be drawn that will lead to insights in the fight against the most recent and rather lethal H7N9 strain.


2020 ◽  
Vol 2 (1) ◽  
pp. 44
Author(s):  
Simuzer Mamedova ◽  
Panagiotis Karanis

Cryptosporidium is an intracellular protozoan parasite and is increasingly gaining attention as a human and an animal pathogen, mainly due to its predominant involvement in worldwide waterborne outbreaks. This paper reviews the current knowledge and understanding of Cryptosporidium spp. in terrestrial and aquatic animals in Azerbaijan. The diagnosis of cryptosporidiosis relies on the identification of oocysts in faecal samples released by the infected host. Stool specimens were processed using the modified acid-fast staining method (Ziehl-Neelsen) and microscopically examined for Cryptosporidium oocysts. Thirteen species of Cryptosporidium (C. fragile, C. ducismarci, C. serpentis, C. varani, C. baileyi, C. meleagridis, C. muris, C. parvum, C. ubiquitum, C. andersoni, C. bovis, C. hominis, C. suis) from amphibians, reptiles, birds and mammals have been identified as a result of studies conducted between 1987 and 2019 on the structural features of Cryptosporidium oocysts in Azerbaijan territory.


2019 ◽  
Vol 21 (1) ◽  
pp. 67 ◽  
Author(s):  
Natalia Fili ◽  
Christopher P. Toseland

Unconventional myosins are multi-potent molecular motors that are assigned important roles in fundamental cellular processes. Depending on their mechano-enzymatic properties and structural features, myosins fulfil their roles by acting as cargo transporters along the actin cytoskeleton, molecular anchors or tension sensors. In order to perform such a wide range of roles and modes of action, myosins need to be under tight regulation in time and space. This is achieved at multiple levels through diverse regulatory mechanisms: the alternative splicing of various isoforms, the interaction with their binding partners, their phosphorylation, their applied load and the composition of their local environment, such as ions and lipids. This review summarizes our current knowledge of how unconventional myosins are regulated, how these regulatory mechanisms can adapt to the specific features of a myosin and how they can converge with each other in order to ensure the required tight control of their function.


Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1035
Author(s):  
Guohui Li ◽  
Xinyu Qi ◽  
Zhaoyang Hu ◽  
Qi Tang

Typical viral propagation involves sequential viral entry, uncoating, replication, gene transcription and protein synthesis, and virion assembly and release. Some viral proteins must be transported into host nucleus to facilitate viral propagation, which is essential for the production of mature virions. During the transport process, nuclear localization signals (NLSs) play an important role in guiding target proteins into nucleus through the nuclear pore. To date, some classical nuclear localization signals (cNLSs) and non-classical NLSs (ncNLSs) have been identified in a number of viral proteins. These proteins are involved in viral replication, expression regulation of viral genes and virion assembly. Moreover, other proteins are transported into nucleus with unknown mechanisms. This review highlights our current knowledge about the nuclear trafficking of cellular proteins associated with viral propagation.


Author(s):  
Magdalena Bachmann ◽  
Weiwei Li ◽  
Michael J. Edwards ◽  
Syed A. Ahmad ◽  
Sameer Patel ◽  
...  

Ion channels allow the flux of specific ions across biological membranes, thereby determining ion homeostasis within the cells. Voltage-gated potassium-selective ion channels crucially contribute to the setting of the plasma membrane potential, to volume regulation and to the physiologically relevant modulation of intracellular potassium concentration. In turn, these factors affect cell cycle progression, proliferation and apoptosis. The present review summarizes our current knowledge about the involvement of various voltage-gated channels of the Kv family in the above processes and discusses the possibility of their pharmacological targeting in the context of cancer with special emphasis on Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv10.1, and Kv11.1.


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