Viroporin potential of the lentivirus lytic peptide (LLP) domains of the HIV-1 gp41 protein.
BACKGROUND
Mechanisms by which HIV-1 mediates reductions in CD4+ cell levels in infected persons are being intensely investigated, and have broad implications for AIDS drug and vaccine development. Virally induced changes in membrane ionic permeability induced by lytic viruses of many families contribute to cytopathogenesis. HIV-1 induces disturbances in plasma membrane ion transport. The carboxyl terminus of TM (gp41) contains potential amphipathic alpha-helical motifs identified through their structural similarities to naturally occurring cytolytic peptides. These sequences have been dubbed lentiviral lytic peptides (LLP) -1, -2, and -3.


RESULTS
Peptides corresponding to the LLP domains (from a clade B virus) partition into lipid membranes, fold into alpha-helices and disrupt model membrane permeability. A peptide corresponding to the LLP-1 domain of a clade D HIV-1 virus, LLP-1D displayed similar activity to the LLP-1 domain of the clade B virus in all assays, despite a lack of amino acid sequence identity.


CONCLUSIONS
These results suggest that the C-terminal domains of HIV-1 Env proteins may form an ion channel, or viroporin. Increased understanding of the function of LLP domains and their role in the viral replication cycle could allow for the development of novel HIV drugs.
Costin
Joshua M
JM
Biotechnology Research Group, Department of Biology, Florida Gulf Coast University, 10501 FGCU Blvd. S., Fort Myers, FL 33965, USA. jcostin@fgcu.edu
Rausch
Joshua M
JM
Garry
Robert F
RF
Wimley
William C
WC
D020816:Amino Acid Motifs; D019295:Computational Biology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides; D040901:Proteomics
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D010455:Peptides; C116049:lentiviral lytic peptide type 1, Human immunodeficiency virus 1