CHOM . . . Huang, etc., reveals multiple protective mechanisms in the bodies of Marburg virus survivors.

Marburg virus is a close relative of Ebola virus and belongs to filovirus.similar to Ebola virus, Marburg virus also causes hemorrhagic fever, which has a high mortality rate. The outbreak in Angola between 2004 and 2005 resulted in 227 deaths, with a mortality rate of 90%.due to the extremely high mortality rate and the lack of effective vaccine and treatment, the two viruses can only be studied in the level 4 biosafety laboratory with the highest safety level.so how does humoral immunity protect patients who are infected with Marburg virus and survive.in 2015, Alexander bukreev team of the University of Texas Medical School and James E. Crowe, Jr. of Vanderbilt University cooperated to publish the article mechanism of human antibody mediated neutralization of Marburg virus on cell. B cells were isolated from convalescent patients infected with Marburg virus, and a series of neutralizing and non neutralizing antibodies were cloned.neutralizing antibody can make the virus lose or reduce its infectivity by binding to different antigen epitopes such as receptor binding site of virus.mr191 is the only neutralizing antibody that can completely protect monkeys after 5 days of virus infection.however, little is known about the role of non neutralizing antibodies in the body of convalescent patients.on April 21, 2020, Alexander bukreyev and James E. Crowe, Jr. team continued to work together (together as Philipp a. ilinykh and Huang Kai) at Cell Host & amp; amp; The article non neutralising antibacterials from a Marburg infection survivor mediate protection by FC effector functions and by enhancing efficiency of other antibodie published in the journal microbe revealed multiple protection mechanisms in survivors of Marburg virus infection.in this study, the researchers found that the non neutralizing antibody mr228 alone could completely protect mice in the infection experiment of mice, indicating that antibody neutralizing virus was not the only factor to protect the survival of patients.although the other non neutralizing antibody mr235 alone can not protect the survival of mice, but in vitro virus neutralization experiments show that the presence of mr235 and other neutralizing antibodies can significantly improve the ability of other antibodies to neutralize viruses, that is, synergistic effect. The IC50 of the half inhibitory concentration is increased by 5-10 times, but mr228 has no such ability.it is speculated that mr235 can better expose the neutralizing site of the virus after binding to the virus, so that other neutralizing antibodies can neutralize the virus better.at the same time, the researchers also found that both mr228 and mr235 could enhance the phagocytosis of neutrophils and monocytes and the activation of natural killer cells.because the above phagocytosis and other effects mediated by antibody are all through the Fc region of antibody, the researchers further modified the Fc region of mr228 to study the protection mechanism of mr228.the researchers constructed recombinant antibodies mr228-ka and mr228-lala. The former can block the binding of antibody to complement C1q and thus block complement activation, while the latter block the binding of antibody to FC γ receptor.animal experiments showed that the recombinant antibody mr228-ka and mr228 prototype could also provide 100% protection, but the protective effect of mr228-lala was significantly decreased, which indicated that the protective mechanism of non neutralizing antibody mr228 was mainly realized through FC γ receptor.further study on the difference of antibody binding ability with mutated virus epitopes and peptide array experiments, the researchers confirmed that the antigen binding epitopes of mr228 and mr235 were in the wing region of the virus GP2, which overlapped but were not identical. through the above experiments, we know that there are multiple protective mechanisms of antibodies in the survival patients infected with Marburg virus. Not only the virus neutralization mechanism is known to us, but also the non neutralizing antibodies can mobilize and enhance the cellular immune function through the Fc region; the non neutralizing antibodies can also show synergistic effect to promote the neutralization of other neutralizing antibodies. original link: