The N-Terminus of the HIV-1 p6 Gag Protein Regulates Susceptibility to Degradation by IDE
Schmalen A, Karius-Fischer J, Rauch P, Setz C, Korn K, Henklein P, Fossen T, Schubert U (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 10
Journal Issue: 12
DOI: 10.3390/v10120710
Abstract
As part of the Pr55(Gag) polyprotein, p6 fulfills an essential role in the late steps of the replication cycle. However, almost nothing is known about the functions of the mature HIV-1 p6 protein. Recently, we showed that p6 is a bona fide substrate of the insulin-degrading enzyme (IDE), a ubiquitously expressed zinc metalloprotease. This phenomenon appears to be specific for HIV-1, since p6 homologs of HIV-2, SIV and EIAV were IDE-insensitive. Furthermore, abrogation of the IDE-mediated degradation of p6 reduces the replication capacity of HIV-1 in an Env-dependent manner. However, it remained unclear to which extent the IDE mediated degradation is phylogenetically conserved among HIV-1. Here, we describe two HIV-1 isolates with IDE resistant p6 proteins. Sequence comparison allowed deducing one single amino acid regulating IDE sensitivity of p6. Exchanging the N-terminal leucine residue of p6 derived from the IDE sensitive isolate HIV-1(NL4-3) with proline enhances its stability, while replacing Pro-1 of p6 from the IDE insensitive isolate SG3 with leucine restores susceptibility towards IDE. Phylogenetic analyses of this natural polymorphism revealed that the N-terminal leucine is characteristic for p6 derived from HIV-1 group M except for subtype A, which predominantly expresses p6 with an N-terminal proline. Consequently, p6 peptides derived from subtype A are not degraded by IDE. Thus, IDE mediated degradation of p6 is specific for HIV-1 group M isolates and not occasionally distributed among HIV-1.
Authors with CRIS profile
Adrian Schmalen
Professur für Virologie
Christian Setz
Institute of Clinical and Molecular Virology
Ulrich Schubert
Professur für Virologie
Additional Organisation(s)
Involved external institutions
University of Bergen / Universitetet i Bergen
Norway (NO)
Charité - Universitätsmedizin Berlin
Germany (DE)
Norway (NO)
Charité - Universitätsmedizin Berlin
Germany (DE)
How to cite
APA:
Schmalen, A., Karius-Fischer, J., Rauch, P., Setz, C., Korn, K., Henklein, P.,... Schubert, U. (2018). The N-Terminus of the HIV-1 p6 Gag Protein Regulates Susceptibility to Degradation by IDE. Viruses, 10(12). https://dx.doi.org/10.3390/v10120710
MLA:
Schmalen, Adrian, et al. "The N-Terminus of the HIV-1 p6 Gag Protein Regulates Susceptibility to Degradation by IDE." Viruses 10.12 (2018).
BibTeX: Download