Structural biology of HIV assembly

During its replication cycle, HIV-1 assembles an immature virus particle by accumulation of viral proteins underneath the cellular membrane. Upon budding of the assembled proteins through the membrane to release an enveloped, immature virus particle, a set of proteolytic cleavage events promotes dramatic changes in the structural organization of the particle to form the mature, infectious virion (Fig. 1a). The structure of the immature virus is defined by the arrangement of the major viral structural polyprotein Gag (Fig. 1b). In the immature state, Gag forms an incomplete shell positioned underneath the membrane. The genomic RNA is bound to the innermost layer of this protein shell. During maturation Gag is cleaved in five positions (Fig. 1c), leading to a major rearrangement of the virion structure. The mature virus contains a conical capsid core which surrounds a condensed ribonucleoprotein mass (Fig. 1a). The differences between the organization of the immature and the mature virion reflect the different structural requirements of HIV-1 during assembly and budding and during entry and disassembly, respectively. HIV-1 morphogenesis and maturation as well as the role of viral and cellular components in these processes have been discussed in several recent reviews (Cold Spring Harbor Perspectives Med 2(7):a006924, 2012; J Mol Biol 410(4):491-500, 2011; Adv Exp Med Biol 726:441-465, 2012; J Mol Biol 410(4):501-511, 2011; Nat Rev Microbiol 9(7):519-531, 2011; Trends Biochem Sci 36(7):373-380, 2011; J Mol Biol 410(4):534-552, 2011). In this chapter we will briefly introduce structural information on Gag domains, and then focus on the structure of the assembled immature and mature viral particle and structural changes during maturation. We will also introduce some of the structural methods used to obtain this information.