Metapneumovirus: determinants of host range and replication
(Metapneumovirus: determinanten van gastheerspecificiteit en replicatie)
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The general composition of the metapneumovirus genome is similar to that of pneumoviruses but differs in the number of genes and their order in the genome (Figure 2) (237). Metapneumoviruses do not encode the nonstructural proteins NS1 and NS2, and the small hydrophobic (SH) and attachment (G) protein genes follow the fusion (F), M2.1 and M2.2 protein genes, whereas for pneumoviruses this is the other way around. In evolutionary terms, this difference is very striking since recombination for members of the subfamily Pneumovirinae has been observed in a laboratory setting only (218). The 3’ and 5’ ends of the genome consist of short extragenic regions, referred to as the leader and trailer regions, and approximately the terminal 12 nt of the leader and the terminal 12 nt of the trailer are complementary, most likely due to the fact that each contains the basic elements of the viral promoter (21, 57, 163). The 3’ end of the viral RNA (vRNA) directs both replication and transcription, while the 5’ end of the genome contains signals that direct the replication of the antigenome. Each gene is preceded by a gene start (GS) signal at which the synthesis of mRNA initiates. Subsequently, each gene terminates with a semiconserved gene end (GE) signal that directs polyadenylation and termination of the completed mRNA. The genomes of metapneumoviruses consist of non-segmented negative stranded RNA and are smaller (~13.000 kb) than those of pneumoviruses (~15.000 kb) (70). For members of the subfamily Paramyxovirinae, the nucleotide length of each genome is a multiplicity of six (“rule of six”), reflecting a requirement of the nucleocapsid for RNA binding (e.g., binding units of six nucleotides) (34). This rule does not apply for the subfamily Pneumovirinae (201), although the reasons underlying this discrepancy have not been determined.
The research described in this thesis was conducted at the Department of Virology of Erasmus MC, Rotterdam, The Netherlands, with financial support from the framework five grant “Hammocs” from the European Union and MedImmune Vaccines, USA.
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