Poliovirus
Patricia G. Melloy in Viruses and Society, 2023
Although poliovirus has been eliminated for 90% of the world’s population, it is important to note that there are other enteroviruses that are an emerging threat. The enterovirus D68, also known as EV-D68, was first discovered in California in 1962. It is a member of the picornavirus family like poliovirus and displays characteristics of both enteroviruses and rhinoviruses in some respects, since it is primarily a mild respiratory illness that can cause neurological symptoms like acute flaccid myelitis (AFM) involving muscle weakness and paralysis. However, AFM itself is poorly understood. Although research is ongoing, scientists believe that EV-D68 is responsible for most cases of AFM (Cassidy et al. 2018; CDC 2021c; Baggen et al. 2018). The CDC indicates that many cases of AFM began to be reported in the United States in 2014 (CDC 2021c). It is not known why cases of AFM are on the rise. Future studies of the picornavirus family of viruses need to focus not only on polio, but also on the non-poliovirus enteroviruses and how to control infection and/or develop a vaccine against these viruses.
Order Picornavirales
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
Figure 27.2 shows the genomic structure of the Picornavirales families and genera, which are most involved into the 3D and VLP studies. In brief, the Caliciviridae members possess monopartite RNA genome of 7.4–8.3 kb, with a 5′-terminal genome-linked virus protein VPg of 10–15 kDa and 3′-terminal poly(A) tract. The genome is organized into either two or three major ORFs, while a further ORF4 of murine norovirus (MNV) encodes virulence factor VF1 (Vinjé et al. 2019). The Picornaviridae genomic RNA, ranging in size from 6.7 kb to 10.1 kb, commonly contains a single large ORF coding for a polyprotein, whereas a typical picornavirus genome encodes three or four capsid proteins and at least seven nonstructural proteins. The IRES element and the 2A genome region may have been exchanged between the genera. There may be more than one protein produced from the L or 2A genome regions, as well as multiple copies of 3B in the picornavirus genome (Zell et al. 2017). The Secoviridae genomic RNA of total 9.0–13.7 kb size could be mono- or bipartite RNA, as mentioned earlier for CPMV. The genomic RNAs are covalently linked to a small viral genome-linked protein VPg of 2–4 kDa at their 5’ end and have a 3’-terminal poly(A) tract. Each RNA encodes, in most of the cases, a single polyprotein (Thompson et al. 2017).
Enteroviruses
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Enteroviruses are one of the five subfamilies (genera) in the family Picornaviridae. They are found in humans (human enteroviruses) and many animals and are species specific. The Picornaviridae are small RNA viruses, thus the term “picornavirus” was derived from “pico,” meaning very small, and “RNA” for the type of genomic nucleic acid. There are over 100 recognized enterovirus serotypes specific for humans (Table 17.1). The enteroviruses share a number of characteristics. They replicate at 37°C, lack a lipid envelope, and are stable at acid pH, which allows them to survive and replicate in the gastrointestinal tract. The virion is composed of a positive single strand of RNA of approximately 7400 nucleotides and a 3′ poly-A tail [1]. The polyprotein is translated into one long single protein, which is then cleaved to form all the individual viral proteins [2]. The capsid is an icosahedron (spheroidal) that is 22–30 nm in diameter and composed of four proteins. Three of them, VP1, VP2, and VP3, are each repeated 60 times and compose the external surface of the capsid. Once the virus completes the replication cycle it is generally released from the host cell via cell lysis, thus killing the infected cell. However, recent studies suggest that a solely lytic infection is not always the case in that the virus or at least viral RNA may persist for months or years after the acute infection [3].
The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease
Published in International Reviews of Immunology, 2023
Shane Prenzler, Santosh Rudrawar, Mario Waespy, Sørge Kelm, Shailendra Anoopkumar-Dukie, Thomas Haselhorst
Rhinoviruses, single-stranded RNA viruses belong to the Picornaviridae family. Rhinovirus is believed to manipulate the expression of Siglec-1 on DCs by induction [25]. The induction of Siglec-1 expression on DCs results in an increased interaction between Siglec-1 and CD43 on T-cells impeding any adaptive immune response [25]. DCs that have undergone induction of Siglec-1 interfere with the appropriate recognition and activation of the T-cell from the antigen presenting cell [25]. Under normal circumstances CD43 receptors on T-cells relocate away to the opposite pole from the synapse between the antigen presenting cell and the T-cell allowing for interaction and activation of the T-cell [25]. Other inhibitory receptors are also present and upregulated during rhinovirus infection such as B7-H1 [25]. However, antibody studies showed that blocking of B7-H1 does not restore function of dendritic cells for the activation of T-cells and that both Siglec-1 and B7-H1 are required antibody blockade to see a restoration of function [25]. It is thought that such dysregulation of the adaptive immune system may increase the frequency of complications to rhinovirus such as otitis media, sinusitis, pneumonia and bronchitis [25, 55].
Therapeutic targets for enterovirus infections
Published in Expert Opinion on Therapeutic Targets, 2020
Mira Laajala, Dhanik Reshamwala, Varpu Marjomäki
Enteroviruses belong to the family of small non-enveloped positive-sense RNA viruses called picornaviridae. The genus enterovirus consists of 15 different species out of which four enterovirus species (EV-A, EV-B, EV-C, and EV-D) and three rhinovirus (RV) species (RV-A, RV-B, and RV-C) infect humans [7]. In addition, there are eight enterovirus species that infect other mammals. Human enterovirus species include over 100 serotypes of echoviruses, polioviruses, coxsackieviruses (CV), and enteroviruses. Moreover, another 100 serotypes are included in the rhinovirus species and also new serotypes within the enterovirus genus are emerging all the time. Despite their prevalence, currently, there are no antivirals on the market to treat enteroviral infections. In addition, vaccines have been produced only against poliovirus and enterovirus 71 (EV-A71), and because of the large amount of different serotypes, the production of vaccines against all enteroviruses is not feasible. Also, vaccines are not available equally around the globe. Instead, the development of broad-spectrum antivirals targeting several serotypes has been the focus on the enterovirus field recently. One of the main challenges in antiviral development is the high mutation rate of enteroviruses that may rule out potential antiviral candidates. In addition, toxicity issues have prevented further development of some effective antivirals [8].
Recent progress and challenges in drug development to fight hand, foot and mouth disease
Published in Expert Opinion on Drug Discovery, 2020
Ze Qin Lim, Qing Yong Ng, Justin Wei Qing Ng, Vikneswari Mahendran, Sylvie Alonso
In 2016, Li and colleagues screened a natural products library containing 502 compounds, and three hits against EV-A71, namely Auraptene, Formononetin, and Yangonin, were identified [83]. All three compounds were found to inhibit EV-A71 infection not only at the attachment stage, but also at a post-attachment stage. Through the selection of escape mutant viruses, it was shown that Auraptene targets the main viral capsid VP1, while Formononetin and Yangonin target VP4 at two different sites [83]. Site-directed mutagenesis in VP1 or VP4 resulted in drug resistance against these compounds, further supporting that they are the targets of these drugs [83]. While Auraptene provided protection against CV-A16 and two EV-A71 clinical strains, Formononetin and Yangonin displayed antiviral activity only against the two EV-A71 isolates [83]. None of them showed any antiviral activity against other members of the Picornaviridae family including CV-B3, PV1, and EV-D68, suggesting that these compounds selectively target HFMD-causing enteroviruses [83].
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