Lentivirus

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Lentivirus (lenti-, Latin for "slow") is a genus of slow viruses of the Retroviridae family, characterized by a long incubation period. Lentiviruses can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lentiviruses.

Interestingly, lentiviruses are capable of infecting neighboring cells in direct contact with the host cells, without having to form extracellular particles.

[edit] Classification

Five serogroups of lentiviruses are recognized, reflecting the vertebrate hosts with which they are associated (primates, sheep and goats, horses, cats, and cattle). The primate lentiviruses are distinguished by the use of CD4 protein as receptor and the absence of dUTPase. Some groups have cross-reactive gag antigens (e.g., the ovine, caprine and feline lentiviruses). Antibodies to gag antigens in lions and other large felids indicate the existence of other viruses related to FIV and the ovine/caprine lentiviruses. Description is on taxonomic level of genus.

[edit] Morphology

Virions enveloped; slightly pleomorphic; spherical; 80-100 nm in diameter. Surface projections of envelope small (surface appears rough), or barely visible; spikes (of about 8nm); dispersed evenly over all the surface. Nucleocapsids (cores) isometric. Nucleoid concentric and rod-shaped, or shaped like a truncated cone.

[edit] Genome Organization and Replication

Features of the genome: infectious viruses have 4 main genes coding for the virion proteins in the order: 5´-gag-pro-pol-env-3´. There are additional genes depending on the virus (e.g., for HIV-1: vif, vpr, vpu, tat, rev, nef) whose products are involved in regulation of synthesis and processing virus RNA and other replicative functions. The LTR is about 600nt long, of which the U3 region is 450, the R sequence 100 and the U5 region some 70 nt long.

Genomic nucleic acid not infectious.

[edit] 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.

[edit] Biological

• Symptoms and Host Range: Host of virus belongs to the Domain Eucarya. Host of virus belongs to the Kingdom Animalia. Phylum Chordata. Subphylum Vertebrata. Class Mammalia. Order Primates, Perissodactyla, Carnivora, and Artiodactyla.

• Transmission: Transmitted by means not involving a vector.

• Geographic Distribution: World-wide.

[edit] 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 irradiation

Classed as having class c morphology

• Nucleic Acid
  • Virions contain 2 % nucleic acid
  • Genome consists of a dimer
  • Virions contain one molecule of (each) linear positive-sense single stranded RNA.
  • Total genome length is of one monomer 9200 nt
  • Genome sequence has terminal repeated sequences; long terminal repeats (LTR) (of about 600 nt
  • The 5' end of the genome has a cap
  • Cap sequence of type 1 m7G5ppp5'GmpNp
  • 3' end of each monomer has a poly (A) tract; 3'-terminus has a tRNA-like structure (and accepts lysin)
  • Encapsidated nucleic acid solely genomic
  • 2 copies packed per particle (held together by hydrogen bonds to form a dimer).
• Proteins 11
  • Virions contain 60 % protein
  • Five structural virion proteins found (major)
  • Protein size 120000 Da
  • Gp120 glycosylated surface envelope protein SU, encoded by the viral gene env
  • Protein size of 2nd largest 41000 Da. Gp41 glycosylated transmembrane envelope protein TM, also encoded by the viral gene env. Protein size of 3rd largest 24000 Da. P24 non-glycosylated capsid protein CA. Protein size of 4th largest 17000 Da. P17 non-glycosylated matrix protein MA. Protein size of 5th largest 7000-11000 Da. Non-glycosylated capsid protein NC. Proteins MA, CA and NA are all encoded by the gag gene. Virion structural proteins are glycosylated. Are the following: the envelope proteins SU and TM. Usually four non-structural proteins found, or three non-structural proteins found (in the primate lentiviruses). Protein size 66000 Da. Reverse transcriptase RT encoded by the pol gene. Protein size of 2nd largest 32000 Da. Integrase IN also encoded by the pol gene. Protein size of 3rd 14000 Da. Protease PR encoded by the pro gene. dUPTase DU, role unknown.
• Lipids: Virions contain 35 % lipid.
• Carbohydrates: Other compounds detected in the particles 3% carbohydrates.

[edit] Practical innovations

Lentiviruses have been successfully used for transfection of diabetic mice with the gene encoding PDGF (platelet-derived growth factor) pubmed,pubmed, a therapy being considered for use in humans. Not only has infection by Lentivirus proven effective, it has not shown some of complications presented by other viruses used for gene therapy.

[edit] References

• Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill. ISBN 0-8385-8529-9.

[edit] External links

• ICTV taxonomy of Lentivirus