[R01] HIV-1 Matrix and Envelope Protein Interactions
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2031-05-31
Importo max: 708.281 EUR
Paese: US
Descrizione
It is important to characterize how HIV-1 proteins fulfill their functions in order to develop new approaches for
curtailing the AIDS epidemic. One of the remaining frontiers of HIV-1 research concerns the mechanisms by
which the HIV-1 matrix (MA) and envelope (Env) proteins collaborate with each other to ensure the assembly
of infectious viruses. The HIV-1 MA protein directs the delivery of precursor Gag (PrGag) proteins to the
plasma membranes (PMs) of infected cells, and drives the formation of lipid raft-like, liquid ordered (Lo)
membrane domains. This membrane reorganization attracts a number of proteins that favor lipid raft-type
microdomains. Such proteins appear to assemble into virus particles as innocent bystanders, and this appears
to be how Env proteins that carry cytoplasmic tail deletions (CT) can be incorporated into virions. In contrast,
wild type (WT) Env proteins additionally require an interaction with MA proteins to assemble into viruses. This
is most easily understood in the context of the lattice that MA proteins construct at the PMs of infected cells. In
particular, multiple lines of evidence imply that the CTs of WT Env proteins are trapped by MA lattices in
immature, assembling virus particles, and then are released after assembled viruses are processed into their
mature forms. Despite a seeming consensus on the MA-Env interaction steps, there are a number of very
significant unknowns. Using our recent and preliminary results as a foundation, and taking advantage of the
unique expertise of our collaborators, we propose the characterization of WT and mutant MA lattices, and of
interactions of MA and Env with each other, and with membrane lipids. Our results will help clarify how MA and
Env cooperate; they will illuminate aspects of host cell protein-membrane interactions; and they will foster the
development of new approaches to intefere with HIV-1 replication.
Istituzione: OREGON HEALTH & SCIENCE UNIVERSITY
PI: ERIC W BARKLIS
Progetto: 1R01AI197883-01A1
Settori: National Institute of Allergy and Infectious Diseases
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