Infection by microsporidia disrupts the host cell cycle

Microsporidia of the genus Encephalitozoon infect mammalian cells and have become a source of morbidity and mortality in immunocompromised humans. Enc ephalitozoon microsporidia develop and mature within parasitophorous vacuol es, enlarging the vacuole over time until it eventually occupies most of th e cytoplasm of the host cell. The ability of the host cell to accommodate s uch a large burden for several days suggests that the parasite subverts nor mal host cell processes to ensure optimal environmental conditions for its growth and development. Since this environment would be threatened if cell division of the host cell occurred, we have formulated the hypothesis that infection with Encephalitozoon microsporidia induces an arrest in the cell cycle of the host cell. In support of this hypothesis, we have found that m itotic index and DNA duplication are reduced in infected cells as compared to uninfected cells. The number of host cell nuclei in S phase is increased . The levels of cyclin D1 and the percentage of cells in G1 are reduced; ho wever, the levels of cyclin B1 are elevated even though the percentage of c ells, in G2/M is decreased. These results suggest that host cells infected with Encephalitozoon microsporidia are blocked at multiple points in the ce ll cycle.