Overexpression of fasciculation and elongation protein ζ-1 (FEZ1) induces a post-entry block to retroviruses in cultured cells

Mojgan H. Naghavi, Theodora Hatziioannou, Guangxia Gao, Stephen P. Goff*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Two mutant Rat2 fibroblast cell lines, R3-2 and R4-7, have been previously isolated by a selection for retrovirus resistance. We have now further analyzed the basis of the block to retroviral infection in the R3-2 line. Using Affymetrix GeneChip analysis, several genes were identified as differentially expressed in the mutant R3-2 line compared with the wild-type cells. One of the candidate gene products, FEZ1 (fasciculation and elongation protein ζ-1), a protein kinase C (PKC)ζ-interacting protein homologous to the Caenorhabditis elegans synaptic transport protein UNC-76, was found to be up-regulated >30-fold in the resistant R3-2 line. FEZ1 overexpression in Rat2 cells conferred a potent resistance to infection by genetically marked retroviruses, and the degree of retroviral resistance in both Rat2 fibroblasts and 293T cells tightly correlated with the expression level of FEZ1 transcripts. FEZ1-overexpressing Rat2 cells showed a similar phenotype to that of the mutant R3-2 line: Infection resulted in normal viral DNA synthesis but a reduction in the formation of circular DNA, indicating a block after reverse transcription but before nuclear entry. Partial knockdown of FEZ1 expression in R3-2 by RNA interference (RNAi) significantly reduced the resistance of this line to infection. Thus, our data suggest that FEZ1 overexpression is sufficient to explain the resistant phenotype of R3-2 cells and identify FEZ1 as a new gene capable of causing retrovirus resistance.

Original languageEnglish (US)
Pages (from-to)1105-1115
Number of pages11
JournalGenes and Development
Volume19
Issue number9
DOIs
StatePublished - May 1 2005

Keywords

  • Cellular factors
  • FEZ1
  • Retroviruses
  • Viral block

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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