Replication of Viruses Infecting Eukaryotes

Abstract

Viruses are biological entities incapable of existing in a cell‐independent manner. Viruses infecting eukaryotic cells offer all possibilities of genome composition, being either DNA or RNA, single‐stranded or double‐stranded, circular or linear, segmented or non‐segmented. Therefore, viruses have evolved a variety of replication strategies to convert viral genome information into infectious viral particles. Furthermore, gene expression strategies affecting replication, transcription, translation, signalling or macromolecular trafficking, have evolved to exploit and subvert the cellular machinery. The cellular response to virus infection is dependent on the gene expression strategies exploited by the different type of viruses. Conversely, to counteract the cellular antiviral response, viruses have developed sophisticated mechanisms leading to a large heterogeneity in the nature of virus‐host interactions. Their study is providing key information for designing strategies of virus control. At the same time, viruses are useful molecular tools to delineate the mechanisms behind basic cellular processes.

Key Concepts:

  • Capsid: A protein shell comprising the main structural unit of a virus particle.

  • Matrix protein: A structural protein of a virus particle that underlies the envelope and links it to the core.

  • Monocistronic: A messenger RNA that encodes a single protein.

  • Negative strand: The group of RNA viruses whose genome contains the reverse polarity of the messenger RNA.

  • Nucleocapsid: The core of a virus particle consisting of the genome plus a complex of proteins.

  • Polyprotein: A long polypeptide encoding several mature proteins that are subsequently released by protease cleavage.

  • Positive strand: The group of RNA viruses whose genome contains the same polarity as the messenger RNA.

  • Receptor: A molecule on the surface of a cell that is used by a virus for attachment.

  • Segmented genome: The group of viruses with the genome packaged in the capsid split into two or more molecules.

  • Uncoating: The stage of viral replication at which structural proteins are disassembled and the virus genome is exposed to the replication machinery.

Keywords: DNA virus; RNA virus; virus–host interaction; viral proteins; virus gene expression

Figure 1.

DNA virus replicative cycle. Early/late gene expression (transcription) and DNA replication can occur either in the cytoplasm or in the nucleus of the infected cell.

Figure 2.

Strategies of genomic organization of different DNA viruses. Examples are given for viruses with a single‐stranded DNA genome, either (a) linear (Parvoviridae) or (b) circular (Geminiviridae), and with a double‐stranded DNA genome, either (c) linear (Adenoviridae) or (d) circular (Papovaviridae). Messenger RNA transcripts are indicated by arrows, with the arrowhead at the 3′‐terminus and the spliced‐out intron sequences shown by angled thin lines.

Figure 3.

Gene expression strategy of picornaviruses. Vpg, 5′‐genome‐linked protein; polyA, polyadenylate sequence at 3′ end. The internal ribosome entry site (IRES) located in the 5′‐UTR guide ribosomes to initiate internally at the AUG start codon of the single open reading frame (ORF; shown in brown). Cotranslational proteolytic cleavages occur due to two viral proteases: L and 3C in aphthovirus, 2A and 3C in entero‐ and rhinovirus. The L or 2A activity act autolytically in cis (grey arrows); 3C cleavages occur first in cis and then in trans (black arrows). Cleavage of the P1, P2 or P3 protein precursors to render mature structural and nonstructural proteins is depicted schematically. Assembly of VP0, VP3 and VP1 in 12 pentamers form icosahedral procapsids. Complete assembly requires genomic RNA, accompanied by autolytic cleavage of VP0 into VP4 and VP2. P2 and other polyprotein precursors act as auxiliary factors for RNA replication by the RdRp (3Dpol); newly transcribed molecules contain a covalently bound 3B (VPg) peptide.

Figure 4.

Expression strategy of the Tobacco mosaic virus (TMV) genome. Solid boxes depict ORFs, shown in different colours. The 5′ ends of the viral mRNAs have a 7‐methylguanosine triphosphate (m7Gppp) cap structure; the 3′‐tRNA‐like sequence of all RNAs is shown as a cloverleaf structure. The ORF near the 5′ end of genomic RNA is translated into a 126‐kDa protein. A ‘leaky’ stop codon allows translational readthrough (1/10 times) to give a 183‐kDa protein. These proteins, together with (a) host factor(s) constitute the RdRp replicase that transcribes a full‐length RNA(–) from genomic RNA(+). The RdRp can also transcribe the RNA(–) into RNA(+), and two nested subgenomic mRNAs by recognition of two or more ‘RNA promoter’ sequences within the RNA(–) sequence. Only the 5′‐proximal ORF of each mRNA is translated.

Figure 5.

(a) Gene expression strategy of the Mononegavirales. The genomic 3′ end is a free –OH group; the 5′ end is phosphorylated but uncapped. The conserved leader sequence is approximately 50 bases. Intergenic polyU sequences of 4–7 bases are conserved. The ORFs are shown in different colours. N/NP are nucleoproteins which bind viral (–) and (+) sense RNA; NS proteins are nonstructural proteins; M or matrix protein is bound by assembled nucleocapsids and binds the cytoplasmic portion of the G/GP membrane glycoproteins, which span the cell‐derived envelope in the assembled virions; the L protein is the RdRp, which is incorporated into virions. (b) Expression strategy of bunyaviruses. All viruses have three genomic ssRNA(–) components: L, M and S, coding for polymerase (L), glycoproteins (G1, G2) and nonstructural (NSm), and nucleoprotein (N) and nonstructural (NSs) proteins, respectively. ORFs are shown in different colours. Only bunyaviruses have an extra NSs (small nonstructural protein) ORF internal to the N ORF; tospoviruses and phleboviruses have an ambisense (both (+) and (–) sense ORFs) S component, with an mRNA being transcribed off the RNA(+) form of the genome. Tospoviruses in addition have an ambisense M component, with the extra 5′‐ORF coding for a host‐derived movement protein (MP).

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Gutierrez, Crisanto, and Martínez‐Salas, Encarnacion(Sep 2009) Replication of Viruses Infecting Eukaryotes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021993]