uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Mapping of the CXCR4 binding site within variable region 3 of the feline immunodeficiency virus surface glycoprotein.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy. (Botling)
Show others and affiliations
2008 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 82, no 18, 9134-42 p.Article in journal (Refereed) Published
Abstract [en]

Feline immunodeficiency virus (FIV) shares with T-cell tropic strains of human immunodeficiency virus type 1 (HIV-1) the use of the chemokine receptor CXCR4 for cellular entry. In order to map the interaction of the FIV envelope surface unit (SU) with CXCR4, full-length FIV SU-Fc as well as constructs with deletions of extended loop L2, V3, V4, or V5 were produced in stable CHO cell lines. Binding studies were performed using these proteins on 3201 cells (CXCR4(hi) CD134(-)), with or without the CXCR4 inhibitor AMD3100. The findings established that SU binding to CXCR4 specifically requires the V3 region of SU. Synthetic peptides spanning the V3 region as well as a panel of monoclonal antibodies (MAbs) to SU were used to further map the site of CXCR4 interaction. Both the SU V3-specific antibodies and the full-length V3 peptide potently blocked binding of SU to CXCR4 and virus entry. By using a set of nested peptides overlapping a region of SU specifically recognized by CD134-dependent neutralizing V3 MAbs, we showed that the neutralizing epitope and the region required for CXCR4 binding are within the same contiguous nine-amino-acid sequence of V3. Site-directed mutagenesis was used to reveal that serine 393 and tryptophan 394 at the predicted tip of V3 are required to facilitate entry into the target cell via CXCR4. Although the amino acid sequences are not identical between FIV and HIV, the ability of FIV to bind and utilize both feline and human CXCR4 makes the feline model an attractive venue for development of broad-based entry antagonists.

Place, publisher, year, edition, pages
2008. Vol. 82, no 18, 9134-42 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-176101DOI: 10.1128/JVI.00394-08PubMedID: 18596086OAI: oai:DiVA.org:uu-176101DiVA: diva2:534276
Available from: 2012-06-15 Created: 2012-06-15 Last updated: 2012-06-15

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Disciplinary Domain of Medicine and Pharmacy
In the same journal
Journal of Virology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 137 hits
ReferencesLink to record
Permanent link

Direct link