Influenza Viral RNA Transcription and Replication

In the host cell nucleus, the viral negative-strand RNA (vRNA) serves as a template for the synthesis both of capped, polyadenylated viral messenger RNA and of full-length positive-strand RNA or complementary RNA (cRNA). The cRNA is associated with the same viral proteins as the vRNA. It serves as a template for the synthesis of new vRNA molecules, which in turn serve as a template for mRNA particularly early in infection, and cRNA. Viral RNA polymerase subunits (PB1, PB2, and PA) and nucleoprotein (NP) enter the host cell nucleus and catalyze all three of these reactions. During initial infection, these proteins enter the nucleus as part of the viral RNP complex. After the first round of viral mRNA synthesis (primary transcription) and translation, newly synthesized viral polymerase proteins and NP localize to the nucleus to catalyze further mRNA transcription and vRNA/cRNA replication. Late in the infection process, the synthesis of vRNA and nuclear export of newly synthesized vRNP (vRNA complexed with NP and viral polymerase) is increased relative to transcription (Krug, 1981; Braam, 1983; Kawakami, 1983; Huang, 1990; Cros, 2003; Fodor, 2004; Deng, 2005; Amorim, 2006; reviewed in Neumann, 2004; Engelhardt, 2006; Buolo, 2006).

在宿主细胞核内，病毒负链RNA（vRNA）充当了合成带帽、多聚腺苷酸化病毒信使RNA以及全长正链RNA或互补RNA（cRNA）的模板。cRNA与vRNA关联的病毒蛋白相同，并作为合成新vRNA分子的模板，而新合成的vRNA分子又作为mRNA（特别是在感染初期）和cRNA的模板。病毒RNA多聚酶亚基（PB1、PB2和PA）以及核蛋白（NP）进入宿主细胞核，催化这三种反应。在初次感染期间，这些蛋白作为病毒RNP复合体的一部分进入细胞核。在第一轮病毒mRNA合成（初级转录）和翻译之后，新合成的病毒多聚酶蛋白和NP定位于细胞核，催化进一步的mRNA转录和vRNA/cRNA复制。在感染后期，vRNA的合成以及新合成的vRNP（vRNA与NP和病毒多聚酶结合的复合物）的核输出相对于转录增加（Krug, 1981；Braam, 1983；Kawakami, 1983；Huang, 1990；Cros, 2003；Fodor, 2004；Deng, 2005；Amorim, 2006；参见Neumann, 2004；Engelhardt, 2006；Buolo, 2006）。