Variant Surface Protein GP60 Contributes to Host Infectivity ofCryptosporidium parvum

Abstract

Biological studies of the determinants of Cryptosporidium infectivity and virulence are lacking despite the fact that cryptosporidiosis is a major public health problem. Here we have used advanced genetic tools to investigate the processing, fate and function of the 60-kDa glycoprotein (GP60), an immunodominant variable antigen associated with protection against reinfection. Endogenous gene tagging revealed that GP60 is highly expressed in sporozoites, merozoites and male gametes, suggesting that it may be involved in both invasion and sexual replication. GP60 is translocated to the parasite membrane and cleaved at the furin cleavage site into GP40 and GP15. During invasion, GP40 translocates to the apical end of the zoites and remains detectable at the parasite-host interface. Although GP60 is dispensable, both gene deletion and replacement reduce parasite growth and severity of infection. Depletion of either GP40 or GP15 alone has less effect. These findings advance our understanding of the parasite-host interaction and pathogenesis of cryptosporidiosis.