RESUMO
The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the Pneumoviridae multifunctional RNA polymerases. In recent months, several high-resolution structures of apo RNA polymerases of Pneumoviridae, which includes the human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), have been determined by single-particle cryo-EM. These structures illustrated high similarities and minor differences between the Pneumoviridae polymerases and revealed the potential mechanisms of the Pneumoviridae RNA synthesis.
Assuntos
Microscopia Crioeletrônica , RNA Polimerases Dirigidas por DNA/ultraestrutura , Pneumovirus/enzimologia , Humanos , Vírus Sincicial Respiratório Humano/enzimologiaRESUMO
The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these viruses are multi-functional complexes, capable of transcribing subgenomic capped and polyadenylated mRNAs and replicating the genome. Although there is no native structure available for any complete paramyxo- or pneumovirus polymerase, functional and structural studies of a fragment of a pneumovirus polymerase protein and mutation analyses and resistance profiling of small-molecule inhibitors have generated a wealth of mechanistic information. This review integrates these data with the structure of a related polymerase, identifying similarities, differences, gaps in knowledge, and avenues for antiviral drug development.
Assuntos
Paramyxoviridae/enzimologia , Pneumovirus/enzimologia , RNA Polimerase Dependente de RNA/metabolismo , Análise Mutacional de DNA , Farmacorresistência Viral , Mutação de Sentido Incorreto , Pneumovirus/fisiologia , RNA Polimerase Dependente de RNA/genética , Transcrição Gênica , Replicação ViralRESUMO
We report here the nucleotide sequence of the L gene of avian pneumovirus (APV). This is the second pneumovirus L gene and the second avian paramyxovirus L gene, following that of Newcastle disease virus, to be sequenced. The APV L gene is 6099 nucleotides long and encodes a single large ORF of 2004 amino acids. This makes the APV L protein the smallest to be described for any nonsegmented, negative-strand RNA virus. The protein contains six linear non-contiguous domains, a putative ATP-binding site and four polymerase motifs previously described for the L proteins of negative-strand RNA viruses. Phylogenetic analysis of domain III of 14 different L proteins suggests the pneumoviruses to be as distant in evolutionary terms from the other members of the Paramyxoviridae as are the Filoviridae.