The effects of HHV-8 vMIP-II on SIVmac251 infection and replication competent and incompetent SIVmac239Δ3 vectors

Kevin V. Morris, Joanne Higgins, Xiaoyng Shen, Jonny T. Stine, Niels C Pedersen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Human herpesvirus type 8 vMIP-II has one of the broadest ranges of chemokine receptor binding and therefore a multiplicity of biologic effects, both immunologic and antiviral. These properties make vMIP-II an attractive effector gene to be expressed from gene therapy vectors. The present studies were concerned with both therapeutic approaches: (1) an anti-simian immunodeficiency virus (SIV) biologic, and (2) an effector gene in SIV-based vectors. Regarding its antiviral properties, vMIP-II expressed from bacteria and SIV-based vectors bound the surface of CEMx174 cells and specifically suppressed SIVmac251 infection. A CCR3 monoclonal antibody partially inhibited vMIP-II binding, suggesting that both SIVmac251 and vMIP-II utilize a similar CCR3-like receptor for CEMx174 cell binding. Replication competent SIV-based vectors containing forward and reverse vMIP-II produced neither identifiable vMIP-II nor virions for the first 21 days. Virus replication occurred after this period. Significant sequence alterations in the forward vMIP-II containing replication competent vector transcripts were responsible for the failure of vMIP-II expression. The genetic basis for the initial failure to replicate virus and its later restoration was not determined but appeared in the II-PIMv containing vectors to coincide with deletions and compensatory rearrangements in nef 3′ of the polypurine tract. Cells transfected with SIVmac239Δ3ΔLTR-vMIP-II vectors expressed biologically active vMIP-II that bound CEMx174 cells and suppressed SIVmac251 infection. These data suggest that replication defective SIV vectors expressing immunobiolgic genes such as vMIP-II may prove useful in gene therapies, particularly in augmenting immune responses in chronically infected individuals.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalVirus Research
Volume94
Issue number2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Chemokine receptors
  • HHV-8
  • Lentiviral selective deletions
  • Suppression of SIV
  • vMIP-II

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Virology

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