Lentiviruses

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Lentiviruses
HI-Virion de.svg

HI virus, graphic

Systematics
Classification : Viruses
Area : Riboviria
Empire : Pararnavirae
Phylum : Artverviricota
Class : Revtraviricetes
Order : Ortervirales
Family : Retroviridae
Subfamily : Orthoretrovirinae
Genre : Lentivirus
Taxonomic characteristics
Baltimore : Group 6
Scientific name
Lentivirus
Left
NCBI  Taxonomy: 11646
ViralZone ( ExPASy , SIB): 264
ICTVdB Virus Code : 00.061.1.06

Lentiviruses (singular: Lentivirus) are enveloped single (+) - strand RNA viruses , (ss (+) RNA) and form a genus within the retrovirus family . The name lentiviruses (slow viruses) is derived from the Latin lentus 'slow' , as many of these viruses cause slowly progressing, chronically degenerative diseases. Others do not cause their host to become ill . Lentiviruses are very species- specific and have so far only been found in various mammalian species . Lentiviruses remain in the host for life because they can bypass the defense mechanisms of the immune system . In contrast to the other retroviruses, they can also infect non-dividing eukaryotic cells. The best known representative of the lentiviruses is the human immunodeficiency virus (HIV).

history

1904 was mixed with the Equine Infectious Anemia ( Equine Infectious Anemia ) described the first triggered by lentiviruses disease. However, the equine infectious anemia virus (EIAV) that causes the disease was not discovered until much later.

Maedi Visna disease was first observed in sheep in Iceland in the 1930s and 1940s, and the causative virus was described in the 1950s as the first lentivirus, the Maedi Visna virus , or MVV for short. In this context, the descriptor Björn Sigurdsson also coined the term slow virus infections , which was initially used for various slowly progressing infectious diseases, including scrapie , and which led to the name "lentiviruses".

In 1981 the immunodeficiency disease AIDS was described and two years later the HIV virus causing the disease was discovered at the Pasteur Institute in Paris, which is now the best-studied virus of all. However, AIDS is still not curable and has turned into a pandemic .

Classification

The genus lentivirus is divided into five different subgroups named after the hosts they infect: bovine, equine, ovine / caprine, feline lentiviruses and the primate lentiviruses. These include, for example, the following types:

Bovine Lentiviruses:
Equine lentiviruses:
Feline Lentiviruses:
Ovine / caprine lentiviruses:
Primate Lentiviruses:

EIAV and Jembrana belong to the group of lentiviruses, but unlike most other lentiviruses, they can also cause acute illness.

Differences from other retroviruses and evolutionary development

Lentiviruses differ from other retroviruses in one characteristic feature: in contrast to alpha or gamma retroviruses, for example, they can influence the regulation of their own genes. For this reason they are counted among the complex retroviruses. They are extremely variable in their nucleotide sequence . Due to the absence of an error correction mechanism and the single stranded nature of the RNA genome, they have some of the fastest evolving genomes.

Lentiviruses produce many different mRNAs through alternative splicing , in the case of HIV there are more than 20, while simple retroviruses usually only express two different mRNA variants , one spliced ​​and one unspliced. This allows you to produce at least ten different proteins . The lentiviral genome shows very strong condensation . The tat, rev and env open reading frames overlap in HIV.

construction

Lentiviruses belong to the complex retroviruses. They are enveloped and have a diameter of 80–100 nm. Like all retroviruses, they have three “main genes” in their genome, gag , pol and env , which code for the viral proteins and which in all lentiviruses are in the order 5'- gag -pol-env -3 'are arranged. They also have various additional genes, which are also referred to as accessory genes (English accessory or auxiliary ) and which can differ from lentivirus to lentivirus. These genes or their products are involved in the regulation, synthesis and processing of the viral RNA and in some cases counteract the defense mechanisms of the host cells. For example, HIV-1 contains the accessory genes vif, vpr, vpu, tat, rev and nef. The long terminal repeat region (LTR region) of the lentiviruses is about 600  nucleotides (nt) long, of which the U3 region accounts for about 450 nt, the R region 100 and the U5 region 70 nt. Due to the accessory genes, the genome of the lentiviruses is on average somewhat larger than that of the simple retroviruses.

The transactivators that increase the transcription efficiency of the LTR promoter include Tat, Tax and Tas. Rev and Rex are transactivators that act post-transcriptionally.

nef

nef negative factor is a myristylated intracellular protein that ensures that the CD4 receptor is downregulated and no longer appears on the cell surface.

rev

rev ( regulator of expression of virion proteins ) codes for a 13–19  kDa protein that is present in tetramers or larger aggregates. It accumulates in the cell nucleus and binds to RRE, the rev-responsive element in the viral mRNA, whereby these RNAs are preferentially exported from the nucleus and processed, which results in an increased expression efficiency.

tas

Tas transactivator of spumaviruses , also called Bel1, is a nuclear protein that binds to the BRE element in human spumaviruses around the U3 region of human spumaviruses.

did

tat ( transactivator of transcription ) codes for the Tat proteins, which are the first virus proteins to be produced in the course of the replication cycle . They have the function of increasing the transcription efficiency of the HI virus. Tat binds to the transactivation-responsive region (TAR), which can be found at the 5 'end of the viral transcripts, and brings about improved elongation . Tat is thus an RNA-binding protein; the TAR region is the first RNA enhancer element to be described. Tat proteins are activated by an acetyltransferase , which transfers acetyl residues to lysyl residues of the protein.

vif

vif ( viral infectivity factor ) codes for the Vif protein that binds to the packaged RNA in the virus particle. It has a size of 22–30 kDa and enables the particles to bypass the cellular APOBEC3 defense mechanism of the host cell.

vpr

vpr codes for the viral protein R (Vpr). Vpr is a small, basic protein of 96 amino acids that is conserved in HIV-1, HIV-2 and SIV and is packaged into the virus particles by binding to the Gag polyprotein . In the course of the infection, Vpr has various functions such as an effect on the correctness of reverse transcription, the import of the pre-integration complex into the cell nucleus, the course of the cell cycle, the regulation of apoptosis and the transactivation of HIV LTRs and various host genes.

vpu

vpu ( viral protein u ) was found in the genome of HIV-1 and SIVcpz. It is 80–82 base pairs long and has the function of promoting the release of virus particles in some human cell types. Group M ( major ) HIV-1 Vpu does this by suppressing a cellular virus defense mechanism mediated by the protein tetherin .

vpx

vpx codes for the viral protein X (Vpx). It consists of 104 to 119 amino acids and has a molar mass between 12 and 16 kDa. The protein is packaged into the virus particles.

This gene is only found in the genome of the human lentivirus HIV-2 and in the primate SIVs of the African green monkeys (SIVagm), the macaques (SIVmac), the white-eyed manga (SIVsm) and the mandrill (SIVdrill). In the genome of HIV-1 or the chimpanzee -SIV (SIVcpz), however, vpx is not present. However, vpx is similar to the vpr of HIV-1 and SIVcpz and performs similar functions. vpx was created from vpr in a recombination event in green monkeys.

Replication cycle

The replication cycle of lentiviruses runs like that of all retroviruses, with the peculiarity that lentiviruses have the ability to overcome the nuclear envelope and thus also to infect dormant cells that are not dividing. Entry into the cell nucleus occurs after the pre-integration complex (PIC) has formed in the cytoplasm . Since the nuclear pores are smaller than the PIC, it must be an active transport process. Both cellular and viral proteins are involved in this process.

Biotechnological use

Lentiviruses are used in genetic engineering as viral vectors in order to specifically smuggle genes into target cells and to express them there .

Individual evidence

  1. ↑ a b c d ICTV: ICTV Taxonomy history: Commelina yellow mottle virus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  2. ↑ H. Vallée, H. Carré: Sur la nature infectieuse de l'anémie du cheval . In: Comptes rendus des seánces de l'Académie des Sciences . Series D: Sciences naturelles . tape 139 , 1904, pp. 331-333 (French).
  3. ↑ Slow Viruses from World of Genetics .
  4. ↑ Björn Sigurdsson: Rida, a chronic encephalitis of sheep. With general remarks on infections which develop slowly and some of their special characteristics . In: Br J Vet . tape 110 , 1954, pp. 341-354 (English). Quoted from Massimo Palmarini: A Veterinary Twist on Pathogen Biology . In: PLOS Pathogens . 2007, doi : 10.1371 / journal.ppat.0030012 (English).
  5. ↑ Dezhong Xu, Huimin Sun, Haixia Su, Lei Zhang; Jingxia Zhang, Bo Wang, Rui Xu: SARS coronavirus without reservoir originated from an unnatural evolution, experienced the reverse evolution, and finally disappeared in the world , in: Chinese Medical Journal, Volume 127, No. 13, July 5, 2014, p . 2537-2542, doi: 10.3760 / cma.j.issn.0366-6999.20131328
  6. ^ A b G. Myers, GN Pavlakis: Evolutionary potential of complex retroviruses . In: J. Levy (Ed.): The Retroviridae. Vol. 1 . Plenum Press, New York 1992, pp. 51-105.
  7. ↑ John Brady and Fatah Kashanchi: Tat gets the "green" light on transcription initiation . In: Retrovirology . Volume 2, 2005, p. 69. PMID 16280076 .
  8. ↑ Wilma Dormeyer: The biochemical analysis of protein acetylation using the example of the HIV-1 Tat protein . Dissertation, 2003, Ruhr University Bochum (PDF; 2.2 MB)
  9. ^ E. Le Rouzic, S. Benichou: The Vpr protein from HIV-1: distinct roles along the viral life cycle . In: Retrovirology. 2005, 2:11 .
  10. ^ SJ Neil, T. Zang, PD Bieniasz: Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature . 2008 Jan 16, PMID 18200009 .
  11. ↑ TM Fletcher, 3rd, B. Brichacek, N. Sharova, MA Newman, G. Stivahtis, PM Sharp, M. Emerman, BH Hahn, M. Stevenson: Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2 / SIV (SM) . EMBO J. 1996 Nov. 15, 15 (22): 6155-6165, PMID 8947037 .
  12. ^ Y. Suzuki, R. Craigie: The road to chromatin - nuclear entry of retroviruses. Nat Rev Microbiol . 2007 Mar, 5 (3): 187-96. Review, PMID 17304248 .

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