Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.16 (
HIV-1 protease
)
2,107
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
SERINC3 (serine incorporator 3) and
SERINC5
are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of
SERINC5
.
SERINC5
antagonism occurred in parallel with other Nef activities, including cell surface receptor downregulation, trans-Golgi network targeting of Lck, and inhibition of host cell actin dynamics. Interaction motifs with host cell endocytic machinery and the Nef-associated kinase complex, as well as CD4 cytoplasmic tail/
HIV-1 protease
, were identified as essential Nef determinants for
SERINC5
antagonism. Characterization of antagonism-deficient Nef mutants revealed that counteraction of
SERINC5
occurs in the absence of retargeting of the restriction factor to intracellular compartments and reduction of
SERINC5
cell surface density is insufficient for antagonism. Consistent with virion incorporation of
SERINC5
being a prerequisite for its antiviral activity, the infectivity of HIV-1 particles produced in the absence of a
SERINC5
antagonist decreased with increasing amounts of virion
SERINC5
. At low levels of
SERINC5
expression, enhancement of virion infectivity by Nef was associated with reduced virion incorporation of
SERINC5
and antagonism-defective Nef mutants failed to exclude
SERINC5
from virions. However, at elevated levels of
SERINC5
expression, Nef maintained infectious HIV particles, despite significant virion incorporation of the restriction factor. These results suggest that in addition to virion exclusion, Nef employs a cryptic mechanism to antagonize virion-associated
SERINC5
. The involvement of common determinants suggests that the antagonism of Nef to
SERINC5
and the downregulation of cell surface CD4 by Nef involve related molecular mechanisms.
...
PMID:The Antagonism of HIV-1 Nef to SERINC5 Particle Infectivity Restriction Involves the Counteraction of Virion-Associated Pools of the Restriction Factor. 2768 Nov 40
