Efficient functional pseudotyping of oncoretroviral and lentiviral vectors by Venezuelan equine encephalitis virus envelope proteins

Andrey A. Kolokoltsov, Scott Weaver, Robert A. Davey

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Murine oncoretroviruses and lentiviruses pseudotyped with envelope proteins of alphaviruses have shown great potential in providing broad-host-range, stable vectors for gene therapy. Unlike vesicular stomatitis virus G protein-pseudotyped vectors, they are not neutralized by complement and do not appear to cause significant tissue damage. Here we report the production of murine oncoretroviral and lentiviral vectors pseudotyped with the envelope proteins of Venezuelan equine encephalitis virus (VEEV). When optimized, these pseudotypes achieve titers of 106 CFU/ml, which is 5- to 10-fold higher than for previous vectors pseudotyped with envelope proteins from other alphaviruses. They can also be concentrated or stored frozen without significant loss of infectivity. Consistent with the tropism of the envelope donor, they transduce a broad array of human cell types, including lung epithelial cells, neuronal cells, lymphocytes, and fibroblasts. Infection is blocked by agents that inhibit endosomal acidification and by neutralizing antibodies against VEEV. These observations indicate that the pseudotypes present native epitopes on their surface and enter through a VEEV envelope-dependent, pH-sensitive mechanism. The fact that the pseudotypes are unaffected by sera reactive to other alphaviruses indicates that they may be useful when successive gene therapies are required in the presence of an active immune response. In this case, having an array of alphavirus-based vectors with similar cell tropisms would be highly advantageous. These vectors may also be useful in diagnostic assays in which infectious VEEV is undesirable but immune reactivity to native epitopes is required.

Original languageEnglish (US)
Pages (from-to)756-763
Number of pages8
JournalJournal of Virology
Volume79
Issue number2
DOIs
StatePublished - Jan 2005

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Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Alphavirus
Viral Envelope Proteins
tropisms
Tropism
gene therapy
Genetic Therapy
epitopes
Epitopes
proteins
Active Immunity
Vesiculovirus
Lentivirus
Proteins
Host Specificity
mice
Neutralizing Antibodies
G-proteins
neutralizing antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Efficient functional pseudotyping of oncoretroviral and lentiviral vectors by Venezuelan equine encephalitis virus envelope proteins. / Kolokoltsov, Andrey A.; Weaver, Scott; Davey, Robert A.

In: Journal of Virology, Vol. 79, No. 2, 01.2005, p. 756-763.

Research output: Contribution to journalArticle

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