Abstract
The matrix domain (MA) of human immunodeficiency virus type 1 Pr55Gag is covalently modified with a myristoyl group that mediates efficient viral production. However, the role of myristoylation, particularly in the viral entry process, remains uninvestigated. This study replaced the myristoylation signal of MA with a well-studied phosphatidylinositol 4,5-biphosphate-binding plasma membrane (PM) targeting motif, the phospholipase C-δ1 pleckstrin homology (PH) domain. PH–Gag–Pol PM targeting and viral production efficiencies were improved compared with Gag–Pol, consistent with the estimated increases in Gag–PM affinity. Both virions were recovered in similar sucrose density-gradient fractions and had similar mature virion morphologies. Importantly, PH–Gag–Pol and Gag–Pol pseudovirions had almost identical infectivity, suggesting a dispensable role for myristoylation in the virus life cycle. PH–Gag–Pol might be useful in separating the myristoylation-dependent processes from the myristoylation-independent processes. This the first report demonstrating infectious pseudovirion production without myristoylated Pr55Gag.
Highlights
Substitution of the myristoylation signal of human immunodeficiency virus type 1 Pr55Gag with the phospholipase C-d1 pleckstrin homology domain results in infectious pseudovirion production
The N-terminal region [p17MA, matrix (MA) domain] of human immunodeficiency virus type 1 (HIV-1) Pr55Gag (Gag), a structural protein with multiple roles in the virus life cycle (Swanstrom & Wills, 1997), is covalently modified with a myristyol group that aids in plasma membrane (PM) targeting
We constructed a mutant gag expression plasmid where the myristoylated region of Gag was replaced with the Nterminal pleckstrin homology (PH) domain of phospholipase C-d1 (PLCd1), a well-studied cellular PM-targeting motif that functions to the myristoyl moiety
Summary
PH–Gag–Pol might be useful in separating the myristoylation-dependent processes from the myristoylationindependent processes This the first report demonstrating infectious pseudovirion production without myristoylated Pr55Gag. The N-terminal region [p17MA, matrix (MA) domain] of human immunodeficiency virus type 1 (HIV-1) Pr55Gag (Gag), a structural protein with multiple roles in the virus life cycle (Swanstrom & Wills, 1997), is covalently modified with a myristyol group that aids in plasma membrane (PM) targeting. The N-terminal region [p17MA, matrix (MA) domain] of human immunodeficiency virus type 1 (HIV-1) Pr55Gag (Gag), a structural protein with multiple roles in the virus life cycle (Swanstrom & Wills, 1997), is covalently modified with a myristyol group that aids in plasma membrane (PM) targeting Removal of this region leads to inefficient Gag targeting to the PM, resulting in dramatically reduced virus production (Bryant & Ratner, 1990; Gottlinger et al, 1989; Pal et al, 1990; Zhou et al, 1994).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
