Introduction to Lentivirus Vectors

Lentiviral vectors are developed from RNA viruses that belong to the Retroviridae family. Within the host cell these viruses can synthesize double-stranded DNA (dsDNA) from their RNA genomes using an enzyme known as reverse transcriptase. This DNA can then be integrated into the chromosome of the host cell using another enzyme carried by the virus, known as integrase. Stable integration of the DNA synthesized from the viral genome modifies the host cell, which now synthesizes viral proteins along with host proteins. When the modified host cell divides, the daughter cells retain copies of the viral genes.

Unlike other retroviruses, lentiviral vectors can also infect non-dividing cells. The only cells that lentiviruses cannot gain access to are quiescent cells (in the G0 state). This is because cells in the G0 phase inherently block the reverse transcription step. Examples of lentiviruses include: Human immunodeficiency virus (HIV); Simian immunodeficiency virus (SIV); Feline immunodeficiency virus (FIV); and Equine infectious anemia virus (EIAV).

The lentivirus genome usually comprises of three ORFs:

Gag - Group-specific antigen: Encodes structural proteins that form the viral capsid

Pol - Polymerase: Encodes the reverse transcriptase, protease and integrase enzymes

Env - Envelope: Encodes the viral envelope (surface and transmembrane glycoprotein) proteins

These viruses also have accessory genes, which encode proteins that are responsible for various replicative functions. For example, the HIV genome features the Vif, Vpr, Tat, Rev, Vpu and Nef genes, which encode regulatory and other accessory proteins.

 

Lentivirus Advantages

Some of the advantages of using lentiviral vectors are mentioned below:

  • Lentiviral vectors can infect both dividing and non-dividing cells.
  • These vectors stably integrate the transgene into the target cell without transferring the sequences that encode for proteins that are derived from the packaging virus. This reduces the risk of setting off an adverse immune response inside the patient’s body.
  • Lentiviral vectors can be pseudotyped to broaden their tropism

 

Lentivirus Limitations

The major risks associated with the use of lentiviral vectors are as follows:

  • In some cases, lentiviral vectors may induce oncogenesis through insertional mutagenesis.
  • These vectors have the potential of generating replication competent lentivirus.

In light of the above mentioned concerns and to avoid the risk of lethal human infection, scientists prefer to use non-human lentiviral vectors, such as FIV, SIV and EIAV.