Lentivirus: History and Characteristics

What is Lentivirus?

Lentivirus is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in man and other mammalian species. The best known lentivirus is the Human Immunodeficiency Virus HIV, which causes AIDS. Recently, lentiviruses have been found in monkeys, lemurs, Malayan flying lemur (not a true lemur nor a primate), rabbits, and ferrets. Lentiviruses and their hosts have worldwide distribution. Lentiviruses can integrate a significant amount of viral RNA into the DNA of the host cell and can efficiently infect nondividing cells, so they are one of the most efficient methods of gene delivery. Lentiviruses can become endogenous (ERV), integrating their genome into the host germline genome, so that the virus is henceforth inherited by the host’s descendants.

What makes Lentivirus so special?

Though there are several virus delivery systems available today for gene therapy, lentivirus is considered one of the best methods. Several features make lentivirus preferable especially the ability to infect both dividing and non-dividing cells. Lentiviral vectors can integrate their genetic cargo directly into the chromosome of the target cell but do not transfer sequences that encode for proteins derived from the packaging virus. This is key to preventing an immune response to the cells containing the transfer gene. Finally, lentivirus vectors can be pseudotyped to infect specific or a broad range of targets.

What is the difference between a Lentivirus and a Retrovirus?

Lentiviruses are a subtype of retrovirus. From an experimental standpoint the main difference between lentiviruses and standard retroviruses (γ-retroviruses) is that lentiviruses are capable of infecting non-dividing and actively dividing cell types whereas standard retroviruses can only infect mitotically active cell types. This means that lentiviruses can infect a greater variety of cell types than retroviruses.

Both lentiviruses and standard retroviruses use the gag, pol, and env genes for packaging; however, they are different viruses and thus use slightly different isoforms of these packaging components. Therefore, lentivirus may not be efficiently packaged by retroviral packaging systems, and vice versa.

Lentivirus history and characteristics

The first actual description of a disease caused by a lentiviral agent came from the observation of the equine infectious anemia in France in 1843. Later, a slowly progressive disorder in sheep was noted in Iceland during the 1950s caused by VMV, which represented a severe form of pneumo-encephalopathy. In the 1960s, American researchers determined the etiology of leukemia and lymphosarcoma of cattle the causative factor was a retrovirus (BIV), morphologically similar to VMV.

Several lineages of closely related human and simian immunodeficiency viruses (HIV and SIV, respectively) are found in primates, which can both result in the acquired immunodeficiency syndrome (AIDS). Simian immunodeficiency viruses are branching into the five additional lineages which are named according their host; those are African green monkey, chimpanzee, sooty mangabey, syke and mandrill SIVs.

Primates naturally infected with these viruses usually remain healthy without the development of AIDS-like diseases, but their transmission to humans gave rise to two genetically different viruses (HIV-1 and HIV-2), still closely related to their ancestral species. Both of these viruses can cause AIDS in humans, albeit their viral kinetics and pandemic potential significantly differ.