Structure and function of the influenza virus genome

A previous study of the 12 nucleotide-long influenza A virion RNA promoter has shown that three nucleotides, residues 9 to 11, were crucial for transcription in vitro, although other nucleotides play a significant but less important role. A model for polymerase-promoter recognition was proposed, according to which there were two sites: a binding site at residues 9 to 11 and a regulatory site at or near the site of initiation at residue 1. By studying the effect of point mutations in the promoter on the binding efficiency of the polymerase using a photochemical cross-linking assay, we now show that residues 9 to 12 are crucial for binding. In addition residues 4 to 8, though not as important, are involved in binding, possibly by stabilizing the polymerasepromoter complex. Both PB1 and PB2 apparently play an important role during virion RNA promoter recognition and binding.

Section: Introductionmentioning

confidence: 99%

Photochemical cross-linking of influenza A polymerase to its virion RNA promoter defines a polymerase binding site at residues 9 to 12 of the promoter

Fodor

Seong

Brownlee

1993

“…In virus-infected cells, the genomic RNAs (vRNAs) are transcribed into two different types of RNA, mRNA and complementary RNA (cRNA; the templates for vRNA synthesis) (Hay et al, 1977a; for a review see McCauley & Mahy, 1983). Viral mRNA synthesis in infected cells is catalysed by a complex of three polymerase proteins, PB1, PB2 and PA, which is carried in the virion, being associated with viral nucleocapsids (Horisberger, 1980;Ulmanen et al, 1981;.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the influenza A virus PB2 protein in the regulation of viral gene expression

Mukaigawa

Hatada

Fukuda

et al. 1991

To determine the function(s) of the PB2 protein of influenza A virus, six temperature-sensitive (ts) mutants of A/Udorn/72 (H3N2) virus, each carrying a ts mutation in the PB2 gene, were analysed for virus RNA and protein synthesis. One of the mutants, ICRC27, exhibited unique phenotypes and was characterized in detail. At the non-permissive temperature, 40 °C, the accumulation of mRNA for each genome segment was reduced severely, leading to delayed and reduced synthesis of viral proteins, complementary and viral RNAs (cRNAs and vRNAs). At the permissive temperature, 34 °C, the mutant virus produced severalfold greater concentrations of both mRNAs and cRNAs of PB2, PB1 and PA segments than wild-type virus. The synthesis of the three polymerase proteins and the induction of RNA polymerase activity were also greatly increased. By contrast, the expression of the haemagglutinin (HA) gene was severely suppressed. The over-production of the polymerase mRNAs was not observed during primary transcription, i.e. in the presence of cycloheximide. The ts ÷ revertants oflCRC27 did not exhibit the ts defects and also lost most of the non-ts phenotypes at 34 °C. These observations indicate that the PB2 protein participates not only in the synthesis of viral RNAs, but also in the regulation of viral gene expression, i.e. in the downregulation of the three polymerase genes and the upregulation of the HA gene during secondary transcription.

“…Among the most frequent infections of the upper and lower respiratory tracts in humans are those caused by influenza A virus, an enveloped, negative-sense, singlestranded RNA virus (Skehel & Hay, 1978;Ghendon et al, 1981;McCauley & Mahy, 1983). In a typical year, the virus infects 15-20 % of the population, causing .500 000 deaths worldwide (Thompson et al, 2003;WHO, 2003), but the most frightening effects are seen when new strains of virus emerge, resulting in devastating pandemics (Reid & Taubenberger, 2003).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of low-concentration chlorine dioxide gas against influenza A virus infection

Ogata

Shibata

2008

Influenza virus infection is one of the major causes of human morbidity and mortality. Between humans, this virus spreads mostly via aerosols excreted from the respiratory system. Current means of prevention of influenza virus infection are not entirely satisfactory because of their limited efficacy. Safe and effective preventive measures against pandemic influenza are greatly needed. We demonstrate that infection of mice induced by aerosols of influenza A virus was prevented by chlorine dioxide (ClO2) gas at an extremely low concentration (below the long-term permissible exposure level to humans, namely 0.1 p.p.m.). Mice in semi-closed cages were exposed to aerosols of influenza A virus (1 LD50) and ClO2 gas (0.03 p.p.m.) simultaneously for 15 min. Three days after exposure, pulmonary virus titre (TCID50) was 102.6±1.5 in five mice treated with ClO2, whilst it was 106.7±0.2 in five mice that had not been treated (P=0.003). Cumulative mortality after 16 days was 0/10 mice treated with ClO2 and 7/10 mice that had not been treated (P=0.002). In in vitro experiments, ClO2 denatured viral envelope proteins (haemagglutinin and neuraminidase) that are indispensable for infectivity of the virus, and abolished infectivity. Taken together, we conclude that ClO2 gas is effective at preventing aerosol-induced influenza virus infection in mice by denaturing viral envelope proteins at a concentration well below the permissible exposure level to humans. ClO2 gas could therefore be useful as a preventive means against influenza in places of human activity without necessitating evacuation.