Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins

Chi Lin Lee, Jason Dang, Kye Il Joo, Pin Wang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Lentiviral vectors (LVs) derived from human immunodeficiency virus type 1 (HIV-1) are promising vehicles for gene delivery because they not only efficiently transduce both dividing and non-dividing cells, but also maintain long-term transgene expression. Development of an LV system capable of transducing cells in a cell type-specific manner can be beneficial for certain applications that rely on targeted gene delivery. Previously it was shown that an inverse fusion strategy that incorporated an HIV-1 receptor (CD4) and its co-receptor (CXCR4 or CCR5) onto vector surfaces could confer to LVs the ability to selectively deliver genes to HIV-1 envelope-expressing cells. To build upon this work, we aim to improve its relatively low transduction efficiency and circumvent its inability to target multiple tropisms of HIV-1 by a single vector. We investigated a method to create LVs co-enveloped with the HIV-1 cellular receptor CD4 and a fusogenic protein derived from the Sindbis virus glycoprotein and tested its efficiency to selectively deliver genes into cells expressing HIV-1 envelope proteins. The engineered LV system yields a higher level of transduction efficiency and a broader tropism towards cells displaying the HIV-1 envelope protein (Env) than the previously developed system. Furthermore, we demonstrated in vitro that this engineered LV can preferentially deliver suicide gene therapy to HIV-1 envelope-expressing cells. We conclude that it is potentially feasible to target LVs towards HIV-1-infected cells by functional co-incorporation of the CD4 and fusogenic proteins, and provide preliminary evidence for further investigation on a potential alternative treatment for eradicating HIV-1-infected cells that produce drug-resistant viruses after highly active antiretroviral therapy (HAART).

Original languageEnglish
Pages (from-to)340-350
Number of pages11
JournalVirus Research
Volume160
Issue number1-2
DOIs
StatePublished - Sep 2011

Bibliographical note

Funding Information:
We thank April Tai, Jason Dang and Michael T. Chou for critical reading of the manuscript, and the USC Norris Center Cell and Tissue Imaging Core. This work was supported by a National Institute of Health grant ( R01-AI68978 and P01-CA132681 ). The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: the cDNA of R5-tropic Env from Drs. Yingying Li, Feng Gao, and Beatrice H. Hahn; TZM-b1 cell line from Drs. John C. Kappes and Xiaoyun Wu, and Tranzyme Inc.

Keywords

  • Human immunodeficiency virus
  • Lentivirus
  • Retrovirus
  • Targeted gene delivery

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