ABSTRACT

A retrovirus vector is a spherical particle of approximately 80-100 nm in diameter, enclosed by a lipid bilayer (derived from the host cell plasma membrane) into which the viral envelope protein is inserted. Its internal structure is mainly composed of the products of the viral gag gene. Simple retroviruses have only three genes, gag, pol, and env, while the complex ones, such as HIV-1, encode a number of additional proteins that are involved in expression of the viral genome and enhancement of the viral replication. On infection, its single-stranded RNA genome enters the host cell along with the enzyme, reverse transcriptase, which catalyzes the synthesis of a DNA strand complementary to the viral RNA and degrades the RNA strand of the viral RNA-DNA hybrid replacing it with DNA. The resulting duplex DNA is translocated to the nucleus and incorporated into the host’s genome by an integrase enzyme. The retroviral vector usually

infects dividing cells since the duplex DNA is transported to the nucleus once the nuclear membrane is temporally disassembled during mitosis. This is of great advantage in tumor-specic expression of therapeutic genes. However, lentiviral vectors, most of which have been derived from HIV, can generally transduce nonmitotic cells by harnessing the cellular nuclear transport mechanism. These vectors can be pseudotyped through inclusion of other viral glycoproteins, such as the vesicular stomatitis virus G protein. As a result, they are not restricted to only CD4+ cells but rather can be used to transduce other cell types (Wu and Ataai 2000). The ability of retroviruses to integrate into the host cell chromosome raises the possibility of insertional mutagenesis within the result of oncogene activation and cancer development.