Intra- and intersubtype alternative Pak2-activating structural motifs of human immunodeficiency virus type 1 Nef.
The design of antiviral strategies against human immunodeficiency virus type 1 (HIV-1) has been largely derived from studies of subtype B viruses, although they constitute only 12% of infections worldwide. At 50% of all HIV-1 infections worldwide, subtype C viruses are the most predominant. Here, we present evidence that subtype C Nefs display functional Pak2-activating motifs that differ from those found in subtype B and E Nefs. The identification of multiple Pak2-activating structural motifs that singly affect one Nef activity revealed a functional plasticity that has implications for future drug and vaccine design aimed at HIV-1 Nef and its effects on the deregulation of the immune system.
O'Neill
Eduardo
E
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75390, USA. eduardo.oneill@utsouthwestern.edu
Baugh
Laura L
LL
Novitsky
Vladimir A
VA
Essex
Myron E
ME
Garcia
J Victor
JV
D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D015693:Gene Products, nef / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D054311:nef Gene Products, Human Immunodeficiency Virus; D054462:p21-Activated Kinases
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases