Lentivirus is a genus of retroviruses that can infect both dividing and non-dividing cells by transporting the viral pre-integration complex into the nucleus, allowing integration of the viral genome without requiring mitosis. The name lentivirus ("slow virus") derives from the prolonged interval between infection and disease observed in the viruses from which the genus was originally defined.The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lentiviruses are distributed worldwide, and are known to be hosted in apes, cows, goats, horses, cats, and sheep as well as several other mammals. Lentiviruses can integrate a significant amount of viral complementary DNA 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. They can become endogenous, integrating their genome into the host germline genome, so that the virus is henceforth inherited by the host's descendants.
Classification Five serogroups of lentiviruses are recognized, reflecting the vertebrate hosts with which they are associated (primates, sheep and goats, horses, domestic cats, and cattle). The primate lentiviruses are distinguished by the use of CD4 protein as a receptor and the absence of dUTPase. The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species:
Morphology
The virions are enveloped viruses 80–100 nm in diameter. They are spherical or pleomorphic, with capsid cores that mature to a cylindrical or conical shape. Projections of envelope make the surface appear rough, or tiny spikes (about 8 nm) may be dispersed evenly over the surface.
Genome Lentiviruses contain 2 positive sense, single-strand RNAs that are bound by nucleocapsid proteins. As with all retroviruses, lentiviruses have gag, pol and env genes, coding for viral proteins in the order: 5´-gag-pol-env-3´. Unlike other retroviruses, however, lentiviruses have two regulatory genes, tat and rev. They may also have additional accessory genes depending on the virus (e.g., for HIV-1: vif, vpr, vpu, nef) whose products are involved in regulation of synthesis and processing viral RNA and other replicative functions. The long terminal repeat (LTR) is about 600 nt long, of which the U3 region is 450, the R sequence 100 and the U5 region some 70 nt long.
Replication Retroviruses carry proteins within their capsids, which bind the RNA genome. These proteins are typically involved in the early stages of genome replication, and include reverse transcriptase and integrase. Reverse transcriptase uses the viral RNA genome as a template for the synthesis of a complementary DNA copy. Reverse transcriptase possesses [RNase H] activity for destruction of the RNA-template. Integrase binds both the viral cDNA generated by reverse transcriptase and the host DNA. Tat acts as a trans-activator during transcription to enhance initiation and elongation. The Rev responsive element acts post-transcriptionally, regulating mRNA splicing and transport to the cytoplasm.
Proteome
The lentiviral proteome consists of five major structural proteins and three or four non-structural proteins. Primate lentiviruses lack the dUTPase, so they have three non-structural proteins, whereas all other lentiviruses encode it. Structural proteins listed by size:
Gp120 surface envelope protein SU, encoded by the viral gene env. 120000 Da (daltons). Gp41 transmembrane envelope protein TM, also encoded by the viral gene env. 41000 Da. P24 capsid protein CA, encoded by the viral gene gag. 24000 Da. P17 matrix protein MA, also encoded by gag. 17000 Da. P7/P9 capsid protein NC, also encoded by gag. 7000–11000 Da. The envelope proteins SU and TM are glycosylated in at least some lentiviruses (HIV, SIV), if not all of them. Glycosylation seems to play a structural role in the concealment and variation of antigenic sites necessary for the host to mount an immune system response. Enzymes:
Reverse transcriptase RT encoded by the pol gene. Protein size 66000 Da. Integrase IN also encoded by the pol gene. Protein size 32000 Da. Protease PR encoded by the pro gene (part of pol gene in some viruses). dUTPase DU encoded by the pro gene (part of pol gene in some viruses), the role of which is still unknown. Protein size 14000 Da. Gene regulatory proteins:
Tat: main trans-activator Rev: important for synthesis of major viral proteins Accessory proteins:
Nef: negative factor Vpr: regulatory protein Vif: APOBEC3 inhibitor Vpu/Vpx: unique to each type of HIV p6: part of gag
Antigenic properties Serological relationships: Antigen determinants are type specific and group specific. Antigen determinants that possess type-specific reactivity are found on the envelope. Antigen determinants that possess type-specific reactivity and are involved in antibody mediated neutralization are found on the glycoproteins. Cross-reactivity has been found among some species of the same serotype, but not between members of different genera. Classification of members of this taxon is infrequently based on their antigenic properties.
Epidemiology Host range: the virus's hosts are found in the orders Primates (humans, apes and monkeys), Carnivora (cats, dogs and other carnivores), Perissodactyla and Artiodactyla (single and double-toed hooved mammals). Transmission: transmitted by means not involving a vector. Geographic distribution: worldwide. Age: Discovery of the endogenised lentivirus RELIK in lagomorphs puts the minimum age estimate of lentiviruses to at least 5.7-7 Million years ago, significantly older than previous estimates.
Physicochemical and physical properties General Buoyant density 1.16–1.18 g cm−3 in sucrose Virions sensitive to heat, detergents, and formaldehyde Infectivity not affected by UV irradiation Classed as having class C morphology
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