scholarly journals Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 166
Author(s):  
Christine E. Peters ◽  
Jan E. Carette
Keyword(s):  
Public Health ◽  
Viral Entry ◽  
Host Factors ◽  
Infectious Agents ◽  
Organelle Biogenesis ◽  
Host Proteins ◽  
Cellular Receptors ◽  
Comprehensive Knowledge ◽  
Cellular Machinery ◽  
Cellular Pathways

Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of how non-polio enteroviruses co-opt cellular pathways has greatly increased, revealing intricate host–virus relationships. In this review, we focus on newly identified mechanisms by which enteroviruses hijack the cellular machinery to promote their replication and spread, and address their potential for the development of host-directed therapeutics. Specifically, we discuss newly identified cellular receptors and their contribution to neurotropism and spread, host factors required for viral entry and replication, and recent insights into lipid acquisition and replication organelle biogenesis. The comprehensive knowledge of common cellular pathways required by enteroviruses could expose vulnerabilities amenable for host-directed therapeutics against a broad spectrum of enteroviruses. Since this will likely include newly arising strains, it will better prepare us for future epidemics. Moreover, identifying host proteins specific to neurovirulent strains may allow us to better understand factors contributing to the neurotropism of these viruses.

scholarly journals Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 354
Author(s):  
Chia-Ming Su ◽  
Raymond Robert Richard Rowland ◽  
Dongwan Yoo
Keyword(s):  
Viral Entry ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Viral Pathogenesis ◽  
Respiratory Syndrome Virus ◽  
Receptor Ligand ◽  
Cellular Receptors ◽  
Prrs Virus ◽  
Recent Advances ◽  
Virus Receptors

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.

scholarly journals Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

2020 ◽  
Vol 22 (1) ◽  
pp. 323
Author(s):  
Ramesh Kumar ◽  
Divya Mehta ◽  
Nimisha Mishra ◽  
Debasis Nayak ◽  
Sujatha Sunil
Keyword(s):  
Rna Virus ◽  
Viral Proteins ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Viral Protein Synthesis ◽  
Post Translational Modifications ◽  
Small Proteins ◽  
Cellular Machinery ◽  
Chemical Groups

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

scholarly journals SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Jordana Muñoz-Basagoiti ◽  
Daniel Perez-Zsolt ◽  
Jorge Carrillo ◽  
Julià Blanco ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Viral Entry ◽  
Ebola Virus ◽  
Lessons Learned ◽  
Productive Infection ◽  
Target Cells ◽  
Emerging Viruses ◽  
Highly Pathogenic ◽  
Life Threatening ◽  
Pathogenic Viruses ◽  
Cellular Machinery

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.

scholarly journals Proteomics Approach to the Study of Cattle Tick Adaptation to White Tailed Deer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Marina Popara ◽  
Margarita Villar ◽  
Lourdes Mateos-Hernández ◽  
Isabel G. Fernández de Mera ◽  
José de la Fuente
Keyword(s):  
Animal Health ◽  
Boophilus Microplus ◽  
Host Factors ◽  
Cattle Tick ◽  
Host Proteins ◽  
Tick Feeding ◽  
Blood Digestion ◽  
Cattle Ticks ◽  
Proteomics Approach ◽  
Single Host

Cattle ticks,Rhipicephalus (Boophilus) microplus, are a serious threat to animal health and production. Some ticks feed on a single host species while others such asR. microplusinfest multiple hosts. White tailed deer (WTD) play a role in the maintenance and expansion of cattle tick populations. However, cattle ticks fed on WTD show lower weight and reproductive performance when compared to ticks fed on cattle, suggesting the existence of host factors that affect tick feeding and reproduction. To elucidate these factors, a proteomics approach was used to characterize tick and host proteins inR. microplusticks fed on cattle and WTD. The results showed thatR. microplusticks fed on cattle have overrepresented tick proteins involved in blood digestion and reproduction when compared to ticks fed on WTD, while host proteins were differentially represented in ticks fed on cattle or WTD. Although a direct connection cannot be made between differentially represented tick and host proteins, these results suggested that differentially represented host proteins together with other host factors could be associated with higherR. microplustick feeding and reproduction observed in ticks fed on cattle.

scholarly journals Network-Guided Discovery of Influenza Virus Replication Host Factors

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Emily E. Ackerman ◽  
Eiryo Kawakami ◽  
Manami Katoh ◽  
Tokiko Watanabe ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Replication ◽  
Virus Replication ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Viral Proteins ◽  
Host Factors ◽  
Ppi Network ◽  
Host Proteins ◽  
Influenza Virus Replication

ABSTRACTThe positions of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of virus-regulated pathways (where proteins do not interact with viral proteins), or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining human PPI networks with virus-host PPI data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow, even after the removal of known abundance-degree bias within PPI data. We have isolated a subnetwork of the human PPI network that connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes distinct from those associated with virus-interacting proteins. Selecting proteins based on subnetwork topology, we performed an siRNA screen to determine whether the subnetwork was enriched for virus replication host factors and whether network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins—more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

scholarly journals Molecular Signaling and Cellular Pathways for Virus Entry

ISRN Virology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Pei-I Chi ◽  
Hung-Jen Liu
Keyword(s):  
Signaling Pathways ◽  
Viral Entry ◽  
Virus Entry ◽  
Host Cells ◽  
Target Cells ◽  
Molecular Signaling ◽  
Cellular Processes ◽  
Cellular Pathways ◽  
Host Life ◽  
Endocytic Vesicles

The cell signaling plays a pivotal role in regulating cellular processes and is often manipulated by viruses as they rely on the functions offered by cells for their propagation. The first stage of their host life is to pass the genetic materials into the cell. Although some viruses can directly penetrate into cytosol, in fact, most virus entry into their host cells is through endocytosis. This machinery initiates with cell type specific cellular signaling pathways, and the signaling compounds can be proteins, lipids, and carbohydrates. The activation can be triggered in a very short time after virus binds on target cells, such as receptors. The signaling pathways involved in regulation of viral entry are wide diversity that often cross-talk between different endocytosis results. Furthermore, some viruses have the ability to use the multiple internalization pathways which leads to the regulation being even more complex. In this paper, we discuss some recent advances in our understanding of cellular pathways for virus entry, molecular signaling during virus entry, formation of endocytic vesicles, and the traffic.

Complex multi-system illnesses occurring within a family: Presumptive evidence for an infectious disease process

2020 ◽  
Vol 10 (1) ◽  
pp. 34-36
Author(s):  
W John Martin
Keyword(s):  
Public Health ◽  
Infectious Disease ◽  
Disease Process ◽  
The Elderly ◽  
Chronic Fatigue ◽  
Learning Disorders ◽  
Infectious Agents ◽  
Definitive Evidence ◽  
Fatigue Syndrome ◽  
Neuropsychiatric Manifestations

Society is witnessing an increasing incidence of illnesses with neuropsychiatric manifestations. Prominent examples include autism and learning disorders in children, depression and chronic fatigue syndrome in adults and neurodegenerative diseases in the elderly. Although clinically diverse, all of these illnesses could be contributed to by infectious agents. If so, one might expect to trace the occurrence and progression of various brain damaging illnesses among various family members. An example of this occurring in three generations of a family was unsuccessfully submitted for publication in another journal 2015; in part because of its Public Health implications. It is submitted to this journal because of definitive evidence for the transmission to humans of infectious cellular sequences incorporated into monkey-derived stealth adapted viruses.

The Role of the Public Health Community in Detecting and Responding to Domestic Terrorism Involving Infectious Agents

2014 ◽  
pp. 219-230 ◽  
Author(s):  
James W. LeDuc ◽  
Stephen M. Ostroff ◽  
Joseph E. McDade ◽  
Scott Lillibridge ◽  
James M. Hughes
Keyword(s):  
Public Health ◽  
Domestic Terrorism ◽  
Infectious Agents ◽  
Public Health Community ◽  
The Public ◽  
Health Community

scholarly journals Childhood detention during COVID-19 in Italy: building momentum for a comprehensive child protection agenda

2020 ◽  
Author(s):  
Silvia Logar ◽  
Maggie Leese
Keyword(s):  
Public Health ◽  
Child Protection ◽  
State Responsibility ◽  
Infectious Agents ◽  
Public Health Response ◽  
The Public ◽  
Health Response ◽  
The Government ◽  
Detention Facilities

Abstract Childhood detention represents an integral part of the public health response to the COVID-19 emergency. Prison conditions in Italy put detained minors at grave risk of contracting sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date (29 April 2020), the Italian penitentiary system is housing 161 minors (147 males), most of them in pre-trial custody, as well as 50 children <3 y of age residing with their mothers in detention. Furthermore, the government reported 5265 unaccompanied minor migrants, mainly from Gambia and Egypt. The fundamental approach to be followed in childhood detention during COVID-19 is prevention of the introduction of infectious agents into detention facilities, limiting the spread within the prison and reducing the possibility of spread from the prison to the outside community. This appears challenging in countries like Italy with intense SARS-CoV-2 transmission. The current COVID-19 pandemic shows the need to provide a comprehensive childhood protection agenda, as the provision of healthcare for people in prisons and other places of detention is a state responsibility.

scholarly journals Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 176 ◽  
Author(s):  
Michela Mazzon ◽  
Ana Ortega-Prieto ◽  
Douglas Imrie ◽  
Christin Luft ◽  
Lena Hess ◽  
...  
Keyword(s):  
Viral Entry ◽  
Broad Spectrum ◽  
Well Being ◽  
Screening Strategy ◽  
Life Cycles ◽  
Antiviral Compounds ◽  
Spectrum Activity ◽  
Cellular Pathways ◽  
Broad Spectrum Activity ◽  
Economic Well Being

Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, and chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists can be made available. Broad-spectrum antivirals are drugs with the potential to inhibit infection by viruses from different groups or families, which may be deployed during outbreaks when specific diagnostics, vaccines or directly acting antivirals are not available. While pathogen-directed approaches are generally effective against a few closely related viruses, targeting cellular pathways used by multiple viral agents can have broad-spectrum efficacy. Virus entry, particularly clathrin-mediated endocytosis, constitutes an attractive target as it is used by many viruses. Using a phenotypic screening strategy where the inhibitory activity of small molecules was sequentially tested against different viruses, we identified 12 compounds with broad-spectrum activity, and found a subset blocking viral internalisation and/or fusion. Importantly, we show that compounds identified with this approach can reduce viral replication in a mouse model of Zika infection. This work provides proof of concept that it is possible to identify broad-spectrum inhibitors by iterative phenotypic screenings, and that inhibition of host-pathways critical for viral life cycles can be an effective antiviral strategy.

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