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].
Enterovirus 68 and Human Respiratory Infections
Sunit K. Singh in Human Respiratory Viral Infections, 2014
The length of the enteroviral single-stranded RNA genome is approximately 7.500 bases with a positive polarity. It has one single open reading frame (ORF), which is preceded at the 5′ end by a long noncoding region (NCR) of approximately one-tenth of the total length of the genome, and followed by a short 3′NCR. This 5′NCR is a very complex structural part of the genome with a lot of structured series of branched and unbranched stem structures and pseudoknots.13 The largest and most dominant structure within this part of the genome is the so-called IRES, or internal ribosomal entry site, which is immediately followed by the AUG start codon for the polyprotein. Attached at the 5′ end is a covalently linked protein called VPg, coded by gene segment 3B, allowing a CAP-independent translation process. Since this virus replicates in a eukaryotic cell, only one polyprotein can be synthesized, which is subsequently processed through a series of primary, secondary, and maturation cleavages.13
SARS-CoV-2 Morphology, Genomic Organisation and Lifecycle
Srijan Goswami, Chiranjeeb Dey in COVID-19 and SARS-CoV-2, 2022
The viral genomic RNA then utilises the host cell machinery, primarily the ribosomes, for translating the viral genomic RNA strand in order to generate several open reading frames (ORFs) essential for the virus lifecycle. As the genomic RNA of the coronavirus undergoes the process of translation utilising the host ribosomes, two important polyproteins (among many) are synthesised. These are very large proteins that come from viral genomic RNA. The two polyproteins are named polyprotein-1a (pp1a) and polyprotein-1ab (pp1ab). These two major polyproteins are synthesised through the process of ‘frameshifting' during translation (Figure 2.6). In Figure 2.6, the region designated ORF1a represents open reading frame 1a and ORF1b represents open reading frame 1b. The irregular junction between ORF1a and ORF1b represents the frameshift site (marked with a dotted circle). ORF1a, ORF1b and the frameshift site in between are responsible for the production of the polyproteins. The polyproteins generated are referred to as replicase polyproteins because they play an important role in replication and further transcription. As the translation progresses through ORF1a, pp1a is synthesised.
Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach
Published in Pathogens and Global Health, 2018
Navaneethan Palanisamy, Dario Akaberi, Johan Lennerstrand, Åke Lundkvist
Like other Flaviviruses, the AHFV genome consists of single-stranded, positive-sense RNA of approximately 10.5 kb, and a single open reading frame. The polyprotein is cleaved into three structural proteins (core, prM and envelope) and eight non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B and NS5) by viral and host proteases. The coding sequence is localized between the 5’ and 3’ untranslated regions (UTRs), which are involved in the pathogenicity of the virus [3]. The NS3 region harbors trypsin-like serine protease and helicase domains, while the NS5 region harbors methyl transferase and RNA-dependent RNA polymerase domains. The NS3 protease activity depends on the presence of NS2B as a cofactor [4,5]. AHFV, like all other Flaviviruses, is an enveloped virus. It can be rendered inactive by exposure to 70% ethanol, dessication or thermal denaturation. An earlier study has shown that AHFV can be completely inactivated at 60 °C when incubated for 3 min, or at 56 °C for 30 min [6].
Protease inhibitor therapy for hepatitis C virus-infection
Published in Expert Opinion on Pharmacotherapy, 2018
HCV belongs to the Flaviviridae family and is a small 40–100 nm virus with a lipid envelope and a single-stranded RNA viral genome with around 9600 nucleotides [17–19]. The positive strand RNA genome includes a 5ʹ-noncoding region with an internal ribosome entry site, an open-reading frame that encodes structural (core, envelope 1, 2) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, NS5B, p7) proteins and a 3ʹ-noncoding region. The internal ribosome entry site causes the translation of a polyprotein precursor which is processed into mature structural and nonstructural proteins [20]. The nonstructural NS3-region consists of an N-terminal serine protease and a C-terminal RNA helicase. The NS4A is an important cofactor for the polyprotein maturation. NS4A holds the NS3 protease domain very close to the membrane and serves as a molecular tether that anchors the HCV replication complex at the cellular membrane [18] (Figure 1). NS4A and NS3 both together form a complex imparting proteolysis of the HCV polyprotein, which splits junctions between the nonstructural proteins. The polyprotein itself is required for the replication as well [21]. All NS3 protease inhibitors are linked with the active site of the enzyme [22]. Currently, it is still challenging to design a pan-genotypic NS3 protease inhibitor.
Chikungunya fever: a threat to global public health
Published in Pathogens and Global Health, 2018
Raíza Nara Cunha Moizéis, Thales Allyrio Araújo de Medeiros Fernandes, Paulo Marcos da Matta Guedes, Hannaly Wana Bezerra Pereira, Daniel Carlos Ferreira Lanza, Judson Welber Veríssimo de Azevedo, Josélio Maria de Araújo Galvão, José Veríssimo Fernandes
The acid environment of the endosome causes conformational changes in the viral envelope that expose the E1 peptide, which in turn promotes the fusion between the endosomal membrane and the viral envelope, releasing the nucleocapsids within the cell, followed by breaking the capsid with the release of the viral genome in the cytoplasm. Replication of viral RNA is preceded by its translation into two precursor polyproteins, one non-structural (ns) P123 and one structural (s) P1234. The non-structural polyprotein is processed into mature non-structural proteins by the activity of viral protease and the host cell itself [18]. Mature nsP1 plays an important role in viral replication since it has multiple enzymatic activities including: ATPase and RNA triphosphatase [19], RNA helicase [17] and protease activity [18]. nsP2 acts to neutralize host cell antiviral responses through multiple mechanisms, including the general transcriptional shutdown of the host cell by inducing Rpb1 subunit degradation of RNA polymerase II [20], inhibition of type 1 interferon production (IFNs) by interfering with the JAK/STAT signaling pathway [21,22] and inducing autophagy [23]. nsP3 is part of the replicase unit and is capable of binding to negatively charged polymers, including RNA [24], as well as promoting interactions with numerous cellular proteins including G3BP [25] and amphiphysins [26]. There is evidence that nsP4 acts as RNA-dependent RNA polymerase and catalyzes the formation of negative-sense, genomic and subgenomic viral RNAs [27].