Skip to content

Advertisement

  • Poster presentation
  • Open Access

CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses

  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
BMC Infectious Diseases201414 (Suppl 2) :P69

https://doi.org/10.1186/1471-2334-14-S2-P69

  • Published:

Keywords

  • Chemokine Receptor
  • Viral Antigen
  • Simian Immunodeficiency Virus
  • Immunofluorescence Assay
  • Syncytium Formation

Background

Chemokine receptors (CKRs), CCR5 and CXCR4 function as major coreceptors in human/simian immunodeficiency virus (HIV/SIV) infections. About 20 alternative G protein-coupled receptors (GPCRs) have been identified as minor coreceptors for the viruses. We reported CCR6 as an alternative coreceptor. A five-amino acid shorter isoform of CCR6, namely CKR-L3, was examined for its coreceptor function and described in this report.

Methods

NP-2 cells transduced with CD4-receptor (NP-2/CD4) normally remain resistant to all HIV/SIV infection; however, further introduction of functional coreceptor can make the cells susceptible to the viruses. NP-2/CD4/CKR-L3 cells were produced to examine coreceptor activity of CKR-L3. Viral antigen in infected NP-2/CD4/coreceptor cells was detected by indirect immunofluorescence assay (IFA). The results were validated by detection of syncytia, proviral DNA and by measuring reverse transcriptase (RT) activities.

Results

HIV-2MIR and SIVsmE660 were found to infect NP-2/CD4/CKR-L3 cells. This justifies the coreceptor function of CKR-L3. Viral antigens appeared faster in NP-2/CD4/CKR-L3 cells than in NP-2/CD4/CCR6, indicates that the CKR-L3 carries more efficient coreceptor-activity. Moreover, syncytia formation was sooner, RT release was higher and earlier through CKR-L3 compared to CCR6. Partial sequence analyses of HIV-2MIR and SIVsmE660 replicated through CKR-L3 and CCR6 coreceptor showed some divergence in envelope region compared to the parental CCR5-variant.

Conclusions

Isoform CKR-L3 exhibited coreceptor activity for limited primary HIV/SIV isolates with better efficiency than CCR6-isoform. Amino acid substitutions in the envelope region of the viruses may confer selective pressure towards CKR-L3-use. CKR-L3 with other minor coreceptors may contribute to HIV/SIV pathogenesis including dissemination, trafficking and latency.

Figure 1

Authors’ Affiliations

(1)
Johns Hopkins University, Baltimore, USA

Copyright

© Islam et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement