Two Influenza A Virus-Specific Fabs Neutralize by Inhibiting Virus Attachment to Target Cells, While Neutralization by Their IgGs Is Complex and Occurs Simultaneously through Fusion Inhibition and Attachment Inhibition

AbstractMabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus–cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus–cell fusion inhibition and virus–cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4–0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose–response curve for neutralization by H36 F(ab′)2 resembled that for IgG, although eightfold more F(ab′)2 was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell

Panspermia, Past and Present: Astrophysical and Biophysical Conditions for the Dissemination of Life in Space

Astronomically, there are viable mechanisms for distributing organic material throughout the Milky Way. Biologically, the destructive effects of ultraviolet light and cosmic rays means that the majority of organisms arrive broken and dead on a new world. The likelihood of conventional forms of panspermia must therefore be considered low. However, the information content of dam-aged biological molecules might serve to seed new life (necropanspermia).Comment: Accepted for publication in Space Science Review

Introduction to modern virology

xiv, 516 p. : ill.; 24 c

The evolution of covert, silent infection as a parasite strategy

Many parasites and pathogens cause silent/covert infections in addition to the more obvious infectious disease-causing pathology. Here, we consider how assumptions concerning superinfection, protection and seasonal host birth and transmission rates affect the evolution of such covert infections as a parasite strategy. Regardless of whether there is vertical infection or effects on sterility, overt infection is always disadvantageous in relatively constant host populations unless it provides protection from superinfection. If covert infections are protective, all individuals will enter the covert stage if there is enough vertical transmission, and revert to overt infections after a ‘latent’ period (susceptible, exposed, infected epidemiology). Seasonal variation in transmission rates selects for non-protective covert infections in relatively long-lived hosts with low birth rates typical of many mammals. Variable host population density caused by seasonal birth rates may also select for covert transmission, but in this case it is most likely in short-lived fecund hosts. The covert infections of some insects may therefore be explained by their outbreak population dynamics. However, our models consistently predict proportions of covert infection, which are lower than some of those observed in nature. Higher proportions of covert infection may occur if there is a direct link between covert infection and overt transmission success, the covert infection is protective or the covert state is the result of suppression by the host. Relatively low proportions of covert transmission may, however, be explained as a parasite strategy when transmission opportunities vary