PAPILLOMAVIRUS ASSEMBLY REQUIRES TRIMERIZATION OF THE MAJOR CAPSID PROTEIN BY DISULFIDES BETWEEN 2 HIGHLY CONSERVED CYSTEINES

We have used viruslike particles (VLPs) of human papillomaviruses to s tudy the structure and assembly of the viral capsid. We demonstrate th at mutation of either of two highly conserved cysteines of the major c apsid protein L1 to serine completely prevents the assembly of VLPs bu t not of capsomers, whereas mutation of all other cysteines leaves VLP assembly unaffected. These two cysteines form intercapsomeric disulfi des yielding an L1 trimer. Trimerization comprises about half of the L 1 molecules in VLPs but all L1 molecules in complete virions. We sugge st that trimerization of L1 is indispensable for the stabilization of intercapsomeric contacts in papillomavirus capsids.