Enhancement of viral infection by antibodies and consequences

SUMMARYAntibodies neutralize the infectivity of viruses, but they can also, on the contrary, enhance the infection by these agents. This harmful effect of antibodies has been described in vitro and/or in vivo and concerns both DNA and RNA viruses. The dengue virus, belonging to the Flaviviridae family, has been particularly studied, as well as members of other families of enveloped viruses but also of non-enveloped viruses, in particular viruses of the genus Enterovirus of the Picornaviridae family. Antibodies can enhance the infection of Fcγ receptor (FcγR)-bearing cells as well as cells that do not possess FcγR. Enhancement of infection is achieved because antibodies directed against viruses increase the entry of these agents into cells or inhibit the antiviral immune response. The enhancing activity of antibodies is improved by several factors, such as antibody afucosylation, low antibody affinity, or epitope accessibility, but is also inhibited by specific geometrical arrangements of antibody-virus complexes. The enhancement of viral infection by antibodies may play a role in the pathophysiology of viral diseases and virus-associated chronic pathologies, as well as in the occurrence of epidemics, which was analyzed using mathematical models. In addition, the existence of these enhancing antibodies is considered in the design of active or passive antiviral immunotherapy to fight viruses. This review addresses the issue of enhancement of viral infections by antibodies and their relevance through a critical examination of available arguments provided by in vivo and in vitro studies.