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Chimeric HIV‐1 and HIV‐2 lentiviral vectors with added safety insurance
Author(s) -
Sachdeva Geetanjali,
D'Costa Jenice,
Cho Jang E.,
Kachapati Kritika,
Choudhry Vidita,
Arya Suresh K.
Publication year - 2007
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20767
Subject(s) - viral vector , vector (molecular biology) , virology , lentivirus , biology , human immunodeficiency virus (hiv) , computational biology , genetics , gene , recombinant dna , viral disease
Lentiviruses are unique in their ability to infect both dividing and non‐dividing cells. This makes the vectors derived from them particularly useful for gene transfer into non‐dividing cells, including stem cells. Lentiviral vectors are becoming the vectors of choice for si/shRNA delivery. The utility of the lentiviral vectors will be enhanced if additional elements of safety are built into their design. One safety concern is the generation of replication competent virus by recombination. We reasoned that HIV‐1 and HIV‐2 hybrid or chimeric lentiviral vectors will have added safety insurance in this regard. This is based on the premise that HIV‐1 and HIV‐2 are dissimilar enough in sequence to curtail recombination, yet similar enough to complement functionally. For hybrid vectors, we found that both HIV‐1 and HIV‐2 transfer vector RNAs could be packaged to equivalent titer by the HIV‐1 packaging machinery. However, HIV‐2 packaging machinery was unable to package HIV‐1 transfer vector as well as it did HIV‐2 transfer vector. This non‐reciprocacity suggested that the requirement for HIV‐2 vectors was more stringent and that for HIV‐1 vectors more promiscuous. When the HIV‐1 transfer vector was packaged with the chimeric packaging construct where the leader‐gag region of HIV‐2 was replaced with that of HIV‐1 packaging construct, the titer of the vector went up. This suggests that at least some of the determinants of specificity for vector assembly reside in the leader‐gag region. Incorporation of central polypurine tract (cPPT) and woodchuck post‐transcriptional enhance element (WPRE) into the HIV‐2 vectors had only modest effect on vector titer. Thus, chimeric lentiviral vectors with added safety features can be designed without compromising transduction efficiency. J. Med. Virol. 79:118–126, 2007. © 2006 Wiley‐Liss, Inc.