Lentiviruses

Virions have a shell, a little pleiomorphic , have a spherical shape and a diameter of about 80-100 nm . The protrusions of the viral membrane make the surface uneven. The nucleoid is concentric, rod-shaped or has the appearance of a truncated cone.

The genome of viruses contains three genes that are located in the genomic RNA in this order 5´- gag - pol - env -3´ . The genome also contains auxiliary genes that differ in different viruses (in the case of HIV-1 it is vif , vpr , vpu , tat , rev , nef ). Auxiliary gene products are involved in the regulation of genomic RNA replication. The long terminal repeats are about 600 nucleotides long, the U3 region is 450, the R sequence is 100, and the U5 region is about 70 nucleotides.

Viral proteins such as reverse transcriptase and integrase are involved in the early stages of replication. Reverse transcriptase (revertase) is an RNA-dependent DNA polymerase encoded by the virus genome. Revertase uses the genomic RNA of the virus as a template for the synthesis of a complementary strand of DNA. Reverse transcriptase also has RNase H activity to break down the RNA matrix. Integrase binds to both cDNA synthesized by reverse transcriptase and host DNA. Prior to embedding the virus genome in the host DNA, integrase “processes” long terminal repeats.

Lentiviruses are able to infect neighboring cells in direct contact without the formation of extracellular particles.

Antigenic determinants are strain-specific. The determinants that determine serotype are on the envelope of the virus and are glycoproteins . The classification of lentiviruses is sometimes based on antigenic properties.

• Are common
  • Floating density 1.16-1.18 g / cm³ in sucrose
  • Virions are sensitive to heat, detergents, and formaldehyde .
  • Infectivity does not decrease with radiation exposure.
• Nucleic acids
  • Virions contain about 2% nucleic acids.
  • The genome consists of dimers.
  • Virions contain one molecule of linear single-stranded (+) RNA.
  • The total length of one genome monomer is 9,200 nucleotides.
  • The genome has repeating end sequences; long terminal repeats are about 600 nucleotides.
  • The 5'-end of the genome is capped , the sequence of the cap is m7G5ppp5'GmpNp.
  • The 3'-end of each monomer contains poly (A); The 3'-end has a structure similar to tRNA and binds to lysine .
  • The capsid contains exclusively genomic nucleic acid.
• Squirrels
  • Virions contain 11 different proteins, which make up 60% of the viral particle.
  • Five major structural proteins by molecular weight.
    • 120 kDa . Gp120 glycosylated SU envelope protein encoded by the env viral gene.
    • 41 kDa. Gp41 is a glycosylated TM membrane transmembrane protein encoded by the env viral gene.
    • 24 kDa. P24 non-glycosylated CA capsid protein.
    • 17 kDa. P17 non-glycosylated MA matrix protein.
    • 7-11 kDa. Non-glycosylated NC capsid protein.
      • The MA, CA, and NC proteins are encoded by the gag gene.
  • Sheath proteins SU and TM are glycosylated in at least some lentiviruses (HIV, monkey immunodeficiency virus). Glycosylation appears to play an important role in masking and provide a variety of antigenic sites necessary for the host's immune response.
  • Four non-structural proteins are usually found, of which three are in primitive lentiviruses.
    • Protein size 66 kDa. RT reverse transcriptase encoded by the pol gene.
    • Protein size 32 kDa. Integrase IN, also encoded by the pol gene.
    • Protein size 14 kDa. Protease PR encoded by the pro gene.
    • dUPT is a DU whose function is unknown.
• Lipids : Virions contain about 35% lipids.
• Carbohydrates : Virions contain about 3% sugar.

Lentiviruses are a convenient vector for introducing genes into in vitro systems or animal models. Lentiviral vectors have been successfully used for the delivery of genetic engineering constructs to block the expression of specific genes by the mechanism of RNA interference ^[2] . Expression of short RNAs containing hairpins ( shRNA ) reduces the expression of a given gene and thus allows one to judge the functions of this gene in a model object. Such studies may precede the development of new drugs for the treatment of diseases by blocking the expression of certain genes.

Lentiviral vectors are also used to introduce new genes into human or animal cells. For example, in the case of a model of hemophilia in laboratory mice, expression of wild-type platelet factor VIII leads to the restoration of the normal phenotype ^[3] . The use of lentiviral vectors has some advantages over other gene therapy methods. Lentiviruses infect dividing and non-dividing cells, express a transgene for a long time, and have low immunogenicity. Lentiviruses expressing PDGF (platelet growth factor) have been successfully used to transfect mice with diabetes ^[4] . It is possible that similar methods of gene therapy will be used in future in humans. Vectors based on gammaretroviruses and lentiviruses have been used in more than 300 clinical trials aimed at developing methods for treating various diseases ^[5] .

Classification of lentiviruses into five serotypes is carried out according to vertebrate taxa, which are infected with the corresponding serotypes (primates, sheep and goats, horses, cats, cattle). Primate lentiviruses differ in CD4 receptor and in the absence of the dUTPase enzyme. Some groups have cross-specific gag antigens.

The genus Lentivirus includes in particular the following species ^{[6] [7]} :

Several strains of this virus are known for the monkey immunodeficiency virus, each of which is characteristic of one species of primates: SIV-agm, SIV-cpz, SIV-mnd, SIV-mne, SIV-mac, SIV-sm, SIV-stm.

• Ryan KJ, Ray CG, eds. Sherris Medical Microbiology: An Introduction to Infectious Diseases. - 4th. - New York: McGraw Hill, 2004 .-- ISBN 0-8385-8529-9 .
• Desport, M. (editor). Lentiviruses and Macrophages: Molecular and Cellular Interactions. - Caister Academic Press, 2010 .-- ISBN 978-1-904455-60-8 .
• “Lentiviruses In Ungulates. I. General Features, History And Prevalence ”, Bulgarian Journal of Veterinary Medicine (2006), 9, No 3, 175−181
• Lentiviruses used in gene therapy
• Tim Ravenscroft . Are Lentiviral Vectors on Cusp of Breakout? , Genetic Engineering & Biotechnology News , Mary Ann Liebert, Inc. (June 15, 2008), pp. 54–55. Date accessed July 6, 2008. “(subtitle) Rapidly emerging technology has potential to treat hemophilia, AIDS, and Cancer.”