Zusammenfassung
The HIV-1 transframe protein p6* known to modulate HIV-1 protease activation has been suggested to interact with the viral pathogenicity factor Nef. However, a potential interaction site in p6* has not been mapped so far. To evaluate effects of p6* modification on viral replication in light of Nef function, clustered substitutions were introduced into the central p6* region of the infectious ...
Zusammenfassung
The HIV-1 transframe protein p6* known to modulate HIV-1 protease activation has been suggested to interact with the viral pathogenicity factor Nef. However, a potential interaction site in p6* has not been mapped so far. To evaluate effects of p6* modification on viral replication in light of Nef function, clustered substitutions were introduced into the central p6* region of the infectious provirus NL4-3 and virus growth and composition of the various mutants was analyzed in different cell cultures in the presence or absence of Nef. Whereas clustered p6* substitutions did neither affect particle incorporation of Nef, nor precursor maturation or viral infectivity, a simultaneous substitution of 40 of the total 56 p6* residues significantly diminished viral infectivity and replication in a Nef-independent manner. Furthermore, this extended modification was not capable of rescuing the negative effects of a transdominant Nef mutant on particle production suggesting that the proposed target for Nef interaction in Gag-Pol is located outside the modified p6* region. In sum these data strongly argue against a functional connection of the central p6* region and Nef during viral life cycle. (C) 2009 Elsevier Inc. All rights reserved.
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