Lentiviruses are enveloped RNA viruses found in most of the vertebrates. The most common Lentiviruses used in gene therapy experiments are retroviruses. The virion contains two copies of RNA genome, which are covered by a cone shaped core. The viral genome contains three genes that code for different viral proteins. The gag gene encodes for capsid, matrix, and nucleocapsid protein. The pol gene is a viral polymerase which comprises of proteases, reverse transcriptase and integrase. The env gene encodes for glycosylated envelope protein which mediates the virus entry into the host cell receptor. The viral RNA genome is flanked by long terminal repeats (LTR) sequences which are responsible for packaging of viral RNA genome. Most of the retroviruses lead to persistent infection by integrating to the host cell genome. Lentiviruses also contain two additional proteins tat and rev which take part in transactivation of viral transcription and nuclear export of viral RNA, respectively.

Following the infection virion binds to the host cell receptor and viral genome enters the cell by fusion. Viral RNA is converted into double stranded DNA with the help of enzyme reverse transcriptase. The double stranded DNA then migrates to the nucleus and integrates to the host cell genome by the help of enzyme integrase. This stage of the virus is known as Provirus . The proviral DNA forms new viral genome by using cellular transcription factors. The immature viral proteins are processed by viral proteases, and assemble along with RNA genome to form an infectious virion, which then buds out from the host cell membrane.

Most of the work based on the lentiviral vector focuses on modifying the human immune deficiency virus type 1 (HIV-1). HIV-1 encodes six accessory proteins namely tat, rev, vif, vpr, nef, and vpu in addition to an essential gag, pol , and env proteins (Figure 15.1).