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Biomedical subjects

R G Webster

Publications and source records attributed to R G Webster.

At least 343 records · Page 19Linked to original sources
PubMed1980

Quantitation of influenza virus antigens on infected target cells and their recognition by cross-reactive cytotoxic T cells.

Monoclonal antibody to type-A influenza virus matrix (M)-protein was used to quantitate the appearance of M-protein on abortively infected P815 cells. After 16 h of infection with different type-A viruses, only a low amount of M-protein appears on the surface of infected cells (approximately 10(3) site/cell) in contrast to approximately 10(5) hemagglutinin molecules on each cell surface. However, virus replication is required for M-protein appearance. Analysis of solubilized membranes purified from 16-h-infected cells shows approximately 10(4) M-protein molecule/cell in the plasma membrane, a content that is consistent with the observed low surface expression, and that indicates that most of the M-protein is localized internally. We found no evidence that cross-reactive cytotoxic T cells could recognize M-protein; neither monoclonal antibody or hyperimmune anti-M-protein antiserum could inhibit T cell killing, either alone or in combination with monoclonal anti-H-2 antibody. Taken together, the low level of M-protein appearance and lack of T cell blocking by anti-M-protein antibody leaves doubt that M-protein is the antigen recognized by cross-reactive cytotoxic T cells.

Animals↗
PubMed1980

Influenza viruses: transmission between species.

The only direct evidence for transmission of influenza viruses between species comes from studies on swine influenza viruses. Antigenically and genetically identical Hsw1N1 influenza viruses were isolated from pigs and man on the same farm in Wisconsin, U.S.A. The isolation of H3N2 influenza viruses from a wide range of lower animals and birds suggests that influenza viruses of man can spread to the lower orders. Under some conditions the H3N2 viruses can persist for a number of years in some species. The isolation, from aquatic birds, of a large number of influenza A viruses that possess surface proteins antigenically similar to the viruses isolated from man, pigs and horses provides indirect evidence for inter-species transmission. There is now a considerable body of evidence which suggests that influenza viruses of lower animals and birds may play a role in the origin of some of the pandemic strains of influenza A viruses. There is no direct evidence that the influenza viruses in aquatic birds are transmitted to man, but they may serve as a genetic pool from which some genes may be introduced into humans by recombination. Preliminary evidence suggests that the molecular basis of host range and virulence may be related to the RNA segments coding for one of the polymerase proteins (P3) and for the nucleoprotein (NP).

Animals↗
PubMed1980

Monoclonal antibodies to hemagglutinin and to H-2 inhibit the cross-reactive cytotoxic T cell populations induced by influenza.

The target antigens recognized by the cross-reactive population of cytotoxic T cells on A/USSR/90/77 (H1N1) influenza virus-infected cells was studied with monoclonal antibodies to the H-2k antigen and viral hemagglutinin. The cytotoxic killing of virus-infected cells was differentially inhibited by three monoclonal antibodies to H-2k. Synergistic inhibition of cytotoxic activity was obtained with monoclonal antibodies to H-2 and to some antigenic determinants on the hemagglutinin melecule of A/USSR but not with others. Since target cells infected with other subtypes of influenza A viruses were not inhibited by any of the monoclonal antibodies to A/USSR hemagglutinin, it is suggested that the sites recognized by the cross-reactive cytotoxic T cells were sterically inhibited by the anti-A/USSR monoclonal antibodies. The results suggest that at least one of the target antigens recognized by the cross-reactive population of cytotoxic T cells is located on the hemagglutinin molecule. The present observations are in agreement with cytotoxic T cell recognition of closely situated viral and H-2 determinants.

Agglutinins↗
PubMed1980

Cross-protection and cross-reactive cytotoxic T cells induced by influenza virus vaccines in mice.

Subunit and intact influenza A virus vaccines have been compared with infectious virus in a mouse model for their ability to induce memory for cross-reactive cytotoxic T cell responses and to protect mice from challenge with different subtypes of influenza A virus. There is an overall correlation between secondary cytotoxic T cell responses and cross-protection. The most long-lasting and successful cross-protection was observed after intranasal infection with influenza virus A/X31 (H3 N2) that replicates efficiently in mice and induces high levels of memory for cross-reactive cytotoxic T cell responses. Short-lasting cross-protection and low levels of T cell-mediated cytotoxicity were associated with infection by A/USSR (H1 N1) virus, that replicates to lower titers in mice, or after multiple injections of inactivated whole virus vaccine. No cross-protection to challenge with heterologous influenza virus was detectable after 1-2 injections of HANA influenza subunit vaccine which failed to prime hosts for cytotoxic T cell responses. These findings may have important implications for vaccination strategy. If cytotoxic T cells play a role in the protection of humans from influenza, live attenuated vaccines should be considered instead of the currently recommended inactivated virus or subunit vaccines.

Animals↗