Human Coronavirus Respiratory Infections
Sunit K. Singh in Human Respiratory Viral Infections, 2014
Coronaviruses are enveloped, positive-sense, single-stranded, ribonucleic acid (RNA) viruses in the family Coronaviridae, of the order Nidovirales.1–3 Viral particles are typically 120–160 nm in diameter and the genomic RNA is capped and polyadenylated with an average length of 27–31 kb.4 Virions are composed of a flexible core, formed by the viral RNA and multiple copies of the nucleocapsid (N) protein, surrounded by the viral membrane, which consists of the spike (S), envelope (E), and membrane (M) proteins.1 The S proteins are heavily glycosylated and this feature is necessary for establishment and maintenance of infection.1 The RNA genome contains at least six open reading frames (ORFs). The 5′ end of the genome encompasses ORF 1, which comprises the majority of the genome (approximately two-thirds). ORF1 is subdivided into ORF1a and ORF1b, which are translated to two polyproteins, pp1a and pp1ab (Figure 27.1). Translation of pp1ab follows pp1a after a - 1 frameshift. These are then cleaved into up to 16 viral replicase proteins by the virus-encoded protease 3CLpro.5
Noroviruses: Laboratory Surrogates for Determining Survival and Inactivation
Dongyou Liu in Laboratory Models for Foodborne Infections, 2017
NoVs are small viruses about 27–32 nm in size and round in structure with an icosahedral symmetry. The human norovirus (HNoV) genome contains a single-stranded positive-sense RNA about 7.6 kb in length that is enclosed in a capsid without an envelope [3]. The capsid is made of 90 capsomers protruding from the shell that has 90 dimers of capsid protein. The genome has three open reading frames (ORFs). ORF1 (nucleotides 146–5359) is about 5 kb in size and encodes a ∼200 kDa nonstructural polyprotein. This nonstructural protein is cleaved to produce the N-terminal protein, the enzyme nucleoside triphosphatase, a 3A-like protein, a genome-linked viral protein (VpG), a 3C-like protease, and RNA-dependent RNA-polymerase (RdRp) [4]. ORF2 (nucleotides 5346–6935) is ∼1.8 kb in size and encodes the 57 kDa major structural capsid viral protein VP1; ORF3 (nucleotides 6938–7573) is ∼0.6 kb in size and encodes a small 22 kDa minor viral structural protein, VP2, reported to package the genome into virions [5,6]. The NoV genus at the time of this submission, is composed of five genogroups based on sequence analysis: genogroup I (GI) (prototype Norwalk virus); GII (prototype Snow Mountain virus); GIII (prototype bovine enteric calicivirus); GIV (prototype Alphatron and Ft. Lauderdale viruses); and GV (prototype Murine NoV) [7,8].
Genome
Paul Pumpens in Single-Stranded RNA Phages, 2020
By the metagenomic analysis of the samples collected from a range of ecological niches worldwide, including invertebrates and extreme microbial sediment, Krishnamurthy et al. (2016) have identified partial genome sequences of 122 RNA phage phylotypes that were highly divergent from each other and from the previously described RNA phages. Three partial genomes from this paper, namely AVE000, AVE001, and AVE002, are included in Table 7.1, since they are the longest and clearly demonstrate novel genome organization features. Thus, the genomes AVE000 and AVE001 are at least 4.95 and 5.02 kb long, respectively. The long AVE000 genome can be attributed to the presence of a novel >1.20 kb ORF of unknown function that is 5′ to and partially overlaps the maturation protein. The AVE001 genome is also expanded due to the presence of a strikingly large 2.39 kb ORF containing the maturation domain, which is larger than all the reference RNA phage maturation genes. The AVE002 is the first RNA phage to contain two nonoverlapping ORFs between the maturation and replicase genes, while neither of the two ORFs has discernable similarity to known proteins. While one of these ORFs likely represents the coat protein, the other ORF might represent a novel lysin or have homologous function to the Qβ read-through protein (Krishnamurthy et al. 2016).
Small, but mighty? Searching for human microproteins and their potential for understanding health and disease
Published in Expert Review of Proteomics, 2018
Annie Rathore, Thomas F. Martinez, Qian Chu, Alan Saghatelian
Microproteins are a rapidly expanding class of peptides and small proteins translated from protein-coding small open reading frames (smORFs, less than 100–150 codons in length). Microprotein is a term that refers to peptides and small proteins that are translated from smORFs and can include known genes. Microprotein discovery and characterization reshapes our understanding of proteome composition and reveals new biological pathways [1]. Genomes contain thousands of open reading frames (ORFs), defined as the protein-coding sequence between an in-frame start and stop codon. Annotation of protein-coding ORFs from DNA sequences became paramount as whole-genome sequencing projects reached completion [2]. Excellent computational methods were developed and utilized to define genes, but these tools needed to establish parameters to reduce false positives. For this reason, most genome annotation pipelines required ORFs to be at least 300 nucleotides long (i.e. 100 amino acids) resulting in most smORFs being missed [2]. To get an idea on the challenge of assigning protein-coding genes without a length cutoff, Basarai, Hieter, and Boeke identified ~260,000 smORFs between 2 and 99 codons when plotting all ORFs in the yeast genome [3]. Today, it is clear that smORFs and their corresponding microproteins make up a sizable fraction of the genome and proteome. As new genes, very little is known about the structure and function of microproteins making these genes an incredible opportunity for discovering new biology.
Recent developments of RNA-based vaccines in cancer immunotherapy
Published in Expert Opinion on Biological Therapy, 2021
Elnaz Faghfuri, Farhad Pourfarzi, Amir Hossein Faghfouri, Mahdi Abdoli Shadbad, Khalil Hajiasgharzadeh, Behzad Baradaran
The fundamental structure of IVT mRNA is correspondent to ‘mature’ eukaryotic mRNA. It comprises a protein-coding open reading frame (ORF) flanked at both 5́ end and 3́ end by untranslated regions (UTRs). Furthermore, the ends consist of a 7-methylguanosine (m7G) 5́ cap structure and a 3́ poly(A) tail. The non-coding structures play an essential role in mRNA’s function and integrity. The non-coding structures can be separately modified to optimize mRNA stability, translation capacity, and immunogenicity [15]. Karikó et al. have found that the appearance of altered nucleosides in the endogenous mRNA’s structure (e.g., methylated nucleosides or pseudo-uridine) could substantially decrease its immune-modulating potency. It has also been found that post-translational alterations in the mRNA structure inhibit the endogenous mRNA from the immune system’ recognition. Also, these post-translational alterations cause immune cells to distinguish it from invasive mRNA [16]. The after mentioned discovery has paved the road for developing methods to improve the translation efficiency and durability of mRNA.
Vaccines against gastroenteritis, current progress and challenges
Published in Gut Microbes, 2020
Hyesuk Seo, Qiangde Duan, Weiping Zhang
Unlike rotavirus for which a few vaccines have been prequalified globally or regionally by WHO or individual nations, there is no vaccine licensed for the single-stranded RNA norovirus or other human calicivirus. Norovirus indeed exceeds rotavirus for global disease burden and becomes the most common viral cause of gastroenteritis in developed countries where rotavirus vaccines have been introduced.6,62-65 Norovirus RNA genome consists of three open reading frames (ORFs). One ORF encodes a polyprotein cleaved into seven non-structural proteins (NP1 to NP7), whereas the other two ORFs encode minor capsid protein VP2 and major capsid protein VP1. VP1 is composed of a conservative shell domain (S) and a variable protruding domain (P). Seven norovirus genogroups and 40 genotypes have been identified, among them three genogroups (GI, GII, and GIV) and 29 genotypes are associated with human gastroenteritis.66,67 However, genotype 4 in GII genogroup, GII.4, is by far the most prevalent and is responsible for a majority of acute gastroenteritis cases.68 Therefore, GII.4 along with the initially identified Norwalk virus GI.1 are primarily targeted in norovirus vaccine development.
Related Knowledge Centers
- Eukaryote
- Molecular Biology
- Prokaryote
- Rna
- Start Codon
- Stop Codon
- Transcription
- Translation
- Terminator
- Gene