Inhibition of HIV entry by extracellular glucuronoxylomannan of Cryptococcus neoformans

Cryptococcosis, caused by Cryptococcus neoformans, is the most common opportunistic fungal disease in HIV/AIDS patients. The prognosis of AIDS patients with Cryptococcus infection is very poor. One of the major characteristics in cryptococcosis patients is the presence of high concentrations of the cryptococcal capsule polysaccharide (CCP) in the serum and cerebrospinal fluid. CCP enhances HIV replication in H9 T-cells, but the mechanism is unknown. In this study, we tested whether extracellular glucuronoxylomannan (GXM), a major component of CCP, enhances HIV entry using replication-incompetent HIV and a cell line which expresses a stable amount of CD4 and both of the HIV co-receptors. Extracellular GXM had no effect on cell-cell fusion however; viral entry surprisingly was inhibited by GXM. Hence, any enhancement of replication must be due to an effect that occurs post-entry.