Multi-Gene Family of Major Surface Glycoproteins of Pneumocystis carinii: Full-Size cDNA Cloning and Expression

The major surface glycoprotein (MSG) of Pneumocystis cariniiplays a crucial role in the fatal pneumonia caused by this organismin AIDS patients. A cDNA encoding a full-length MSG polypeptidewas isolated from a phage library of rat-derived P. cariniicDNAs. The deduced MSG, referred to as the MSG5 subtype, isa 120,765-Da protein composed of 1,076 amino acids and containsan anchoring hydrophobic sequence at the C-terminus of the protein.Sequence analyses of cloned MSG-cDNAs revealed an MSG-gene familywith 70% protein sequence identity between subtypes. P. cariniikaryotype hybridization analyses indicated that the MSG genefamily members are scattered throughout most of the P. cariniichromosomes. These recombinant MSG proteins reacted with theantiserum from P. carinii-infected rats, as expected, and antiserumgenerated against P. carinii-infected mice, indicating the existenceof common determinants in MSG polypeptides. The family of MSGproteins is rich in cysteine residues and these cysteine arehighly conserved in all MSG subtypes regardless of species specificity,suggesting the structural and/or functional importance of thesecysteine. The pathobiological significance of the MSG gene familyand its sequence diversity in P. carinii is discussed.