Role of surface glycoproteins in influenza virus pyrogenicity

Abstract

Eleven H3N2, seven H1N1 and three H3N1 influenza virus reassortants of the pyrogenic A/Puerto Rico/8/34-A/England/939/69 clone 7a (H3N2) (A/7A) and poorly pyrogenic A/Fiji/15899/83 (H1N1) (A/Fiji) parents were analysed genetically for the parental origin of their genes and for their pyrogenicity in ferrets. All H3N2 reassortants were pyrogenic and produced significantly more fever than A/Fiji but differences in pyrogenicity between them could not be correlated with either single or constellations of genes. All HIN1 reassortants were poorly pyrogenic compared with A/7A but one (Am29) produced significantly more fever than A/Fiji. No correlation of the increased fever with inserted A/7A genes was evident in Am29 and, while mutations were detected in the HI haemagglutinin of this reassortant using monoclonal antibodies, similar mutations were present in the other H1N1 reassortants which showed no increase in fever production. The three H3N1 reassortants were intermediate in their pyrogenicity, being more pyrogenic than A/Fiji and less pyrogenic than A/7A. Overall, these results support previous conclusions that the haemagglutinin and/or neuraminidase play a major role in the pyrogenicity of influenza virus.

Role of apoptosis and cytokines in influenza virus morbidity

“…Such dsRNA is released from infected cells when they die and thus may stimulate cytokine production in uninfected cells [33]. However, virion components are also pyrogenic as virosomes containing no RNA but including viral lipid, haemagglutinin and neuraminidase induced fever, although less so than virions killed by limited heating or UV‐inactivation, which destroys infectivity without affecting pyrogenicity [34–37]. Individual components were not pyrogenic explaining why whole virus vaccines can produce influenza‐like symptoms while subunit vaccines do not.…”

Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test

“…12 Superantigens Huang et al, 1997a;Huang et al, 1997b;Roggiani et al, 1997 Exotoxins Hackett andStevens, 1992;Fitzgerald and Pastan, 1993;Bhakdi et al, 1994;Houldsworth et al, 1994;Murai et al, 1996 Lipoarabinomannans (from mycobacteria) Carson et al, 1988;Rawadi and Roman-Roman, 1996 Fungal components (e.g., mannans, glucans, mannoproteins) Barwick et al, 1994;Castro et al, 1996 Parasite components (e.g., phosphoinositol) Bate et al, 1989 Viruses Barry et al, 1976;Jakeman et al, 1991;Gong et al, 1991;Becker et al, 1991;Alluwaimi et al, 1994;Chang and Shaio, 1994;Kurokawa et al, 1996;Price et al, 1997 Non-microbiological contaminations (e.g., cytokines, media, Soprana et al, 1994 cells, breakdown products) Solid materials (e.g., medical devices, plastic) Miller and Anderson, 1988 Drugs (e.g., steroids, bile salts, dapsone, cytokines) Beloeil et al, 1980;Bodel and Dillard, 1968;Coleman, 1995 and lipoproteins are all potent cytokine inducers that were able to fulfill at least three of Koch and Dale's criteria to prove their role as cytokine inducers in human cells. the presence of lPS was mostly excluded by the lAl assay.…”

Cytokine induction in human cord blood lymphocytes after pulsing with UV-inactivated influenza viruses

“…These surface receptors are necessary for the recognition of conserved microbial-associated molecular patterns and for the production of pro-inflammatory and immuno-regulatory cytokines early on during an infection [14]. Of the two viral surface proteins, the HA and neuraminidase (NA), both are highly pyrogenic and mitogenic [3,15]. Furthermore, HA is the most abundant surface protein.…”