Research WORKTOPIC:VIRUS REPLICATION COMPLEX FORMATION And FUNCTIONING
Answers
NA and reverse-transcribing viruses. We regret that space limitations prevent highlighting all of the valuable contributions to these fields (Mackenzie, 2005; Miller and Krijnse-Locker, 2008; Novoa et al., 2005; Salonen et al., 2005).
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Explanation:
For many (+)RNA viruses, RNA replication requires viral enzymes such as RdRp, helicase, capping enzymes, and NTPase, as well as non-enzymatic proteins that participate in the assembly of the viral replication complex. Host cell proteins often play essential roles in (+)RNA virus replication as well. (+)RNA virus replication is asymmetric: the synthesis of (+)RNA, the one that is packaged into the progeny virus, is up to ∼100 times greater than that of (−)RNA [1]. Both the structure of the replicase itself and the cis-acting signals in the viral RNA template have been implicated in regulating the relative levels of genomic and antigenomic RNAs.
Host membranes play an important role in (+)RNA virus replication, as the RNA replication complexes released from membranes during purification generally lose the ability to catalyze true RNA replication, although a limited activity may be retained. In general, the intracellular membranes of cells infected with (+)RNA viruses rearrange to form anchor sites for viral RNA replication complexes [2]. Membrane tethering of the replication complexes is facilitated by non-structural proteins with hydrophobic sequences that enable membrane integration or interaction. In picornavirus-infected cells, viral RNA replication occurs on the cytoplasmic surfaces of double-membrane vesicles derived from the endoplasmic reticulum (ER) [3]. Two-dimensional (2D) arrays of polymerase-containing oligomeric structures have been observed on the surface of these vesicles, and the structural integrity of these 2D arrays correlates with the cooperative RNA binding and RNA elongation activities of the polymerase [4]. In cells infected with the flock house virus, outer mitochondrial membranes invaginate to create open-necked spherules of ∼50 nm in size [5]. On average, each spherule contains ∼100 membrane-spanning, self-interacting protein A molecules (i.e., the multifunctional RNA replication factor) and two to four genomic RNA replication intermediates [5]. Membranes may function to expedite the assembly of replication complexes, to protect/sequester viral RNAs, and also to help segregate the products from templates during replication.
While eukaryotic cells sequester and organize their genome replication and transcription in the nucleus, many RNA and some DNA viruses carry out viral genome replication and transcription in the cytoplasm. To establish efficient genome replication and shield it from host defenses, including crucial intrinsic and innate defenses, many or most of these cytoplasmically replicating viruses organize their genome replication and transcription in organelle-like compartments (Novoa et al., 2005). These replication compartments or factories often are associated with the sites of subsequent stages in the viral replication cycle, including particle formation and virus budding.
Recently, substantial advances have been made in characterizing the cytoplasmic replication compartments of positive-strand RNA viruses. Positive-strand RNA viruses package their genomes as messenger sense, single stranded RNA and replicate those genomes solely through RNA intermediates. For a diverse set of positive-strand RNA viruses, three-dimensional, high resolution imaging by electron microscope (EM) tomography, in combination with other complementary approaches, have revealed critical aspects of the structure and organization of membrane-bounded RNA replication compartments and their close spatial and functional relationships with virus translation and virion assembly and budding sites. This review summarizes selected recent findings in this area and their relation to other RNA and DNA viruses, including implications for potential evolutionary relationships between the genome replication processes of at least some positive-strand RNA viruses and those of double strand (ds)R