Viral infections have been suspected of being involved in the pathogenesis of certain autoimmune diseases for many years. Epstein-Barr virus (EBV), a DNA virus belonging to the Herpesviridae family, is thought to be associated with the onset and/or the progression of multiple sclerosis (MS), systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and type 1 diabetes. The lifecycle of EBV consists of lytic cycles and latency programmes (0, I, II and III) occurring in infected B-cells. During this lifecycle, viral proteins and miRNAs are produced. This review provides an overview of the detection of EBV infection, focusing on markers of latency and lytic phases in MS. In MS patients, the presence of latency proteins and antibodies has been associated with lesions and dysfunctions of the central nervous system (CNS). In addition, miRNAs, expressed during lytic and latency phases, may be detected in the CNS of MS patients. Lytic reactivations of EBV can occur in the CNS of patients as well, with the presence of lytic proteins and T-cells reacting to this protein in the CNS of MS patients. In conclusion, markers of EBV infection can be found in MS patients, which argues in favour of a relationship between EBV and MS.

Enteroviruses (EV) initiate replication by binding to their cellular receptors, leading to the uncoating and release of the viral genome into the cytosol of the host cell. Neutralising antibodies (NAbs) binding to epitopes on enteroviral capsid proteins can inhibit this infectious process through several mechanisms of neutralisation in vitro. Fc‐mediated antibody effector functions such as antibody‐dependent cell‐mediated cytotoxicity and antibody‐dependent cellular phagocytosis have also been described for some EV. However, antibody binding to virions does not always result in viral neutralisation. Non‐neutralising antibodies, or sub‐neutralising concentrations of antibodies, can enhance infection of viruses, leading to more severe pathologies. This phenomenon, known as antibody‐dependent enhancement (ADE) of infection, has been described in vitro and/or in vivo for EV including poliovirus, coxsackievirus B and EV‐A71. It has been shown that ADE of EV infection is mediated by FcγRs expressed by monocytes, macrophages, B lymphocytes and granulocytes. Antibodies play a crucial role in the diagnosis and monitoring of infections. They are valuable markers that have been used to establish a link between enteroviral infection and chronic diseases such as type 1 diabetes. Monoclonal and polyclonal antibodies targeting enteroviral proteins have been developed and shown to be effective to prevent or combat EV infections in vitro and in vivo. In addition, vaccines are under development, and clinical trials of vaccines are underway or have been completed, providing hope for the prevention of diseases due to EV. However, the ADE of the infection should be considered in the development of anti‐EV antibodies or safe vaccines.

SUMMARY: Antibodies 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.