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].
Adeno-Associated Virus-Based Delivery Systems
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
Between the two itr are two nonoverlapping open reading frames (orf). As can be seen in Figure 1, the first orf codes for regulatory proteins (22-24), and the second orf codes for structural proteins. The regulatory orf is called the rep gene(s), and the structural orf is labeled the cap gene. There are two promoters at map positions 5 and 19, an intron near the 3' end of the rep genes, and a polyadenylation site at map position 96. This organization produces four different rep genes by splicing mechanisms (reps 78, 68,52, and 40) (25-27). The structural orf uses a promoter, p40, found at map position 40, and produces VP1-3 by splicing in the same frame (16,18,28,29). This basic organization is the same for the autonomous virus genomes that are related to AAV parvoviruses. There is some homology between human parvovirus B19 and AAV in the rep regions, but there is no detectable hybridization between parvoviruses and AAV (30).
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.
Recent advances in human norovirus research and implications for candidate vaccines
Published in Expert Review of Vaccines, 2020
Jordan E. Cates, Jan Vinjé, Umesh Parashar, Aron J. Hall
Noroviruses are classified within the Caliciviridae family, and have a 7.5 kb linear, positive sense, single-stranded RNA genome that is enclosed in a non-enveloped icosahedral capsid [24]. The genome is organized into three open reading frames (ORFs). ORF1 encodes a polyprotein that is co- and post-translationally cleaved into six non-structural viral proteins, including the RNA-dependent RNA polymerase (RdRp). ORF2 encodes VP1, the major structural capsid protein, which is composed of a shell (S) and two protruding (P) regions (P1 and P2). ORF3 encodes VP2, a minor structural capsid protein. Based on sequence differences of the VP1 protein, noroviruses are classified into at least ten genogroups (GI-GX), with most infections in humans caused by GI and GII viruses [25]. Noroviruses can be further classified into genotypes and P (polymerase)-types based on amino acid diversity of VP1 and nucleotide diversity of the RdRp region, respectively. Currently, there are at least 49 genotypes and 60 P-types [25]. Genogroup II genotype 4 (GII.4) viruses are further divided into epidemiologically important variants that carry the name of the location for the first strain from which the complete capsid sequence was submitted to GenBank (e.g., GII.4 Sydney).
Related Knowledge Centers
- Eukaryote
- Molecular Biology
- Prokaryote
- Rna
- Start Codon
- Transcription
- Translation
- Stop Codon
- Terminator
- Gene