+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity

CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity

Antiviral Research 39(3): 175-187

The natural CC-chemokine RANTES(3-68), missing two NH2-terminal residues, has been isolated from leukocytes and tumor cells. The highly specific aminopeptidase dipeptidyl peptidase IV (DPP IV), also called CD26, was shown to be responsible for this NH2-terminal truncation of RANTES. Here it is reported that CD26/DPP IV treatment of RANTES enhances its anti-HIV-1 activity. RANTES(3-68) inhibited infection of PBMC by M-tropic HIV-1 strains ten-fold more efficiently than intact RANTES. This difference in antiviral potency between intact and truncated RANTES was even more pronounced (at least 25-fold) in CCR5-transfected cell lines. In HOS.CD4.CCR5 transfected cells, RANTES(1 - 68) had virtually no anti-HIV-1 activity (IC50 > 130 nM), whereas RANTES(3 - 68) was a potent inhibitor of HIV-1 replication (IC50: 5.5 nM). The anti-HIV-1 activity of RANTES(1-68) in the different cell types correlated with the expression of CD26. Moreover, the addition of soluble CD26 together with RANTES(1-68) significantly enhanced the antiviral activity of RANTES in HOS.CD4.CCR5 cells (IC50: 13 nM). These observations point to an important role of CD26-mediated processing of RANTES in inhibiting the replication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS.

(PDF emailed within 0-6 h: $19.90)

Accession: 010262810

Download citation: RISBibTeXText

PMID: 9833958

DOI: 10.1016/s0166-3542(98)00039-4

Related references

Molecular engineering of RANTES peptide mimetics with potent anti-HIV-1 activity. Faseb Journal 25(4): 1230-1243, 2011

RANTES is required for ischaemia-induced angiogenesis, which may hamper RANTES-targeted anti-atherosclerotic therapy. Thrombosis and Haemostasis 99(4): 794-795, 2008

RANTES is required for ischaemia-induced angiogenesis, which may hamper RANTES-targeted anti-atherosclerotic therapy. 2007

Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. Journal of Biological Chemistry 273(13): 7222-7227, 1998

Amino-terminal truncation of RANTES by CD26/dipeptidyl peptidase IV is required for its activity against M-tropic HIV-1 strains. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 38: 371, 1998

Semisynthetic analogues of PSC-RANTES, a potent anti-HIV protein. Bioconjugate Chemistry 19(2): 480-489, 2008

Structural and functional studies of the potent anti-HIV chemokine variant P2-RANTES. Proteins 78(2): 295-308, 2010

Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1 beta/CCL4. Protein Engineering, Design & Selection 21(2): 65-72, 2008

Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES. Chemistry & Biology 6(1): 43-51, 1999

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes. Genes and Immunity 7(7): 544-549, 2006

Similarities and differences in RANTES- and (AOP)-RANTES- triggered signals: implications for chemotaxis. The Journal of Cell Biology 144(4): 5-65, 1999

Aggregation of RANTES is responsible for its inflammatory properties. Characterization of nonaggregating, noninflammatory RANTES mutants. Journal of Biological Chemistry 274(39): 27505-27512, 1999

Amino-terminally modified RANTES analogues demonstrate differential effects on RANTES receptors. Journal of Biological Chemistry 274(45): 32478-32485, 1999

Association between RANTES promoter polymorphism -401A and enhanced RANTES production in atopic dermatitis patients. Journal of Dermatological Science 39(3): 189-191, 2005

Human eosinophils express RANTES mRNA and store and release biologically active RANTES protein. Journal of Allergy & Clinical Immunology 97(1 PART 3): 243, 1996