The genome of incomplete influenza virus

After three high-multiplicity passages of the WSN strain of influenza virus in primary chick embryo fibroblast monolayers, the virus produced contained much less of the largest RNA segment and reduced amounts of the next two largest segments as compared with normal virus. The double-stranded RNA isolated from the cells which produced these particles also showed a similar decrease in these three segments as did the cRNA, both that associated with polysomes and non-polysome associated. Virions lacking these RNAs did not transcribe these segmentsin vitro but did transcribe the other five segments. An analysis of the molar ratios of segments indicated that the three largest segments are the most seriously affected. There was no evidence for random loss of segments either by these analyses or by our inability to enhance infectivity by clumping defective virions.     

The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus multiplication

Summary Analogues of pyrophosphate have been tested as inhibitors of influenza virus RNA polymerase activity in cell-free assays. The most active compound, phosphonoformic acid (PFA), reduced the polymerase activity to 50 per cent at a concentration of 20 µm. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 µm also inhibited the influenza virus plaque formation by 90 per cent.     

The factors of virulence of influenza a virus

This review deals with factors that influence the virulence of influenza A virus. A high genetic and antigenic variability is demonstrated in a broad spectrum of influenza A viruses ranging from avirulent to lethal ones. Influenza A viruses have caused several epidemics and pandemics in the past and present that have cost millions of lives worldwide. Therefore these viruses still belong to the most important ones with strong impact on whole human population. Here, we discuss the latest findings concerning the role of individual viral proteins, interaction of the virus with the host immune system, and interspecies transmission and evolution of the virus. It is important to elucidate the genetic background of virulence of influenza A viruses, mechanisms involved in crossing the interspecies barrier, and mechanisms of destruction of the host cell by these viruses, and to identify the factors influencing the interaction between these viruses and the host immune defense system. This knowledge should help to estimate the threat of influenza A viruses with human pandemic potential to human population.     

The action of influenza virus on human chromosomes

Bulletin of Experimental Biology and Medicine -     

The immune response of hamsters to purified haemagglutinins and whole influenza virus vaccines following live influenza virus infection

The ability of several, live type A influenza viruses to enhance the serum haemagglutination-inhibiting (HI) antibody response of hamsters to subsequent immunization with inactivated, heterotypic influenza virus vaccines was examined. Live influenza viruses were found to vary in their priming ability for a given vaccine, and a given virus was not able to prime for all inactivated vaccines to an equal extent. Common determinants in the haemagglutinin antigens of the priming virus and the vaccine virus were suggested as responsible for the enhancement of the antibody response to some of the vaccines, but for other pairs of viruses the haemagglutinin antigens were distinct. Thus, enhancement in these instances cannot be due to cross-reacting haemagglutinins. Pre-infection of hamsters by several influenza type A viruses was employed in an attempt to enhance the serum HI antibody response to purified, haemagglutinin antigens prepared from A/PR/8/34 and the MRC-2 recombinant strain of A/England/42/72 viruses. Although prior infection enhanced the antibody response to whole virus, this was not demonstrable for the purified haemagglutinin components of the virus. The possible reasons for this are discussed.     

小鼠感染流感病毒后可抵抗致死性流感病毒攻击的研究

目的 BALB/c小鼠初次感染流感病毒(A/California/7/2009(H1N1)(pCA07)和A/Guangzhou/333/99(H9N2)(GZ333))后,用流感病毒鼠肺适应株A/PR/8/34(H1N1)(PR8) 10倍致死剂量攻击,观察攻毒后小鼠的反应.方法 BALB/c小鼠150只,分成3组,空白对照组PBS滴鼻,实验组分别感染甲型H1N1流感病毒pCA07和禽源H9N2病毒GZ333;感染56 d后用10倍致死剂量的鼠肺适应株流感病毒PR8攻击两个实验组和对照组小鼠,比较PR8病毒攻击后,病毒载量和抗体水平,以及对小鼠存活率的影响.结果 感染过pCA07和GZ333的小鼠在致死病毒PR8攻击后全部存活,并分别在病毒攻击6d和9d后小鼠肺组织中检测不到攻击病毒.对初次感染病毒的抗体水平在病毒PR8攻击后迅速升高,在保持初次感染病毒抗体的同时能够产生针对PR8病毒的抗体.结论 不同亚型流感病毒感染小鼠后可以提供交叉保护.     

The postvaccination antibody response to influenza virus proteins

The radio-immunoblot (RIB) assay was used to examine the antibody response to proteins of the vaccine strains induced after influenza vaccination. Vaccination stimulated an antibody response to the surface glycoproteins (HA and NA) and to the internal antigens (NP and M) of the three vaccine strains. Antibodies were detected to both the monomeric form of the haemagglutinin (HA) and its two subunits HA1 and HA2. In addition, antibody to the monomeric form of NA was detected. A wide range of response patterns was observed to the viral proteins. All three major antibody classes (IgG, IgA and IgM) were induced after vaccination and in the majority of volunteers the antibody reactivity increased one week after vaccination. IgM antibodies had a wider reactivity pattern, recognising proteins and subunits which were not fully processed or slightly degraded. The varied antibody response induced after influenza vaccination reflects the differing infection histories of the volunteers with influenza. We show some of the practical limitations of studying the antibody response to influenza vaccination.     

The amantadine-sensitivity of recombinant and parental influenza virus strains

Several wild-type influenza A strains together with recombinants derived from these strains, were tested for sensitivity to amantadine using the in vitro techniques of inhibition in egg-bit culture and plaque reduction in MDCK cells. The results obtained were analysed with reference to the derivation of the recombinants. Susceptibility to amantadine was related to the gene coding for matrix protein, and these data are in agreement with previous reports of studies using other series of influenza viruses.     

Studies on influenza virus

Summary 1233, Berlin and Jamaica strains of influenza type C virus were examined for their antigenic relationship by haemagglutination inhibition, indirect haemagglutination and complement fixation methods. The strains differed between themselves and the Jamaica virus did so to a much greater degree than the other two. Comparison of amniotic with allantoic derivatives of the virus showed that the antigenic difference between them in the Jamaica strain was more substantial than in Taylor and Berlin strains. Sera collected early in immunization were superior to hyperimmune sera in detecting antigenic variations.     

The genetic aspects of influenza virus filamentous particle formation

Summary We analysed the genetic content of reassortants between parent viruses differing in their ability to form filaments. The results suggest that primarily HA, M, and NP genes are involved in the control of the filament forming ability. A lower buoyant density of the filamentous forms as compared to spherical particles allowed us to obtain a sufficiently pure population of filaments. A difference in the UV-inactivation kinetics between filaments and spherical virions suggests that the infectious filamentous forms are probably represented by multigenomic particles or partial heterozygotes.