Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity

Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for plasmodium falciparum. yet,nearly 20% of infected children die annually as a result of severe malaria. multiple risk factors are postulated to exacerbate malarial disease,one being co-infections with other pathogens. children living in sub-saharan africa are seropositive for epstein barr virus (ebv) by the age of 6 months. this timing overlaps with the waning of protective maternal antibodies and susceptibility to primary plasmodium infection. however,the impact of acute ebv infection on the generation of anti-malarial immunity is unknown. using well established mouse models of infection,we show here that acute,but not latent murine gammaherpesvirus 68 (mhv68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. importantly,this resulted in the transformation of a non-lethal p. yoelii xnl infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center b cells and t follicular helper (tfh) cells in the spleen. furthermore,we have identified the mhv68 m2 protein as an important virus encoded protein that can: (i) suppress anti-mhv68 humoral responses during acute mhv68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. notably,co-infection with an m2-null mutant mhv68 eliminates lethality of p. yoelii xnl. collectively,our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. this suggests that acute infection with ebv should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for plasmodium transmission. © 2015 matar et al.