A neutral glycoprotease of Pasteurella haemolytica A1 specifically cleaves O-sialoglycoproteins.

A neutral metalloprotease with marked specificity for an O-sialoglycoprotein has been isolated from culture supernatants of Pasteurella haemolytica A1. The 35-kDa enzyme cleaves human erythrocyte glycophorin A, which is O glycosylated, but does not cleave N-glycosylated proteins or nonglycosylated proteins. Glycophorin A was cleaved when it was present in situ in erythrocyte ghost plasma membranes or when it was free in solution. The glycoprotease did not hydrolyze glycophorin A from which sialate residues had been removed by neuraminidase treatment. An immobilized preparation of the enzyme cleaved glycophorin A at several positions, with a major site of cleavage at Arg-31-Asp-32. The glycoprotease is inhibited by EDTA, citrate, and ascorbate, but inhibition appears to be due to the masking of metal ion activators rather than to their removal. The enzyme is not inhibited by phosphoramidon, an inhibitor of other bacterial neutral metalloproteases.     

Viral dynamics and their relations to baseline factors and longer term virologic responses in treatment-naive HIV-1-infected patients receiving abacavir in combination with HIV-1 protease inhibitors

From a study of 71 HIV-1-infected patients receiving abacavir in combination with 1 of 5 different HIV-1 protease inhibitors (indinavir, ritonavir, saquinavir, nelfinavir, or amprenavir), we found that the baseline HIV-1 RNA levels were highly predictive of the viral decay rates. The baseline HIV-1 RNA levels were negatively correlated with the first phase viral decay rates (r = -0.77, P < 0.001) and positively correlated with the second phase viral decay rates (r = 0.68, P < 0.001). In addition, the first phase viral decay rate was positively correlated with CD4+ cell increases. No significant correlation was found between viral decay rates and longer term (24 weeks) virologic responses, and no difference in viral decay rates was found among the 5 study regimens. These data suggest that the potency of the 5 treatment regimens was similar and was not predictive of long-term virologic failure.