Lentivirus

Lentiviruses (singular: lentivirus ) are enveloped single ( ) strand RNA viruses ( ss ( ) RNA) and constitute a genus ( genus ) within the family of retroviruses. The term lentiviruses (slow viruses) derives from Latin: lentus = slow down, as many of these viruses cause slowly progressive, chronic degenerative diseases. Others do not cause illness of her host. Lentiviruses are very species - specific and have only been found in various mammalian species. Lentiviruses remain for life in the host because they can bypass defense mechanisms of the immune system. They can not infect actively dividing, eukaryotic cells, in contrast to other retroviruses. Known representative of the lentiviruses human immunodeficiency virus ( HIV).

History

In 1904 described the first triggered by lentivirus disease of contagious equine anemia ( Equine Infectious Anemia ). The virus triggers the disease of equine infectious anemia ( EIAV ), however, was not discovered until much later.

In the 1930s and 1940s the Maedi - Visna disease was observed in sheep in Iceland for the first time, the causative virus was abbreviated MVV described in the 1950s as the first lentivirus maedi - visna virus. In this context, was coined by the descriptor Bjorn Sigurdsson, the term slow virus infections, which was initially used for various slowly progressive infectious diseases, including scrapie and the " lentiviruses " led to the designation.

In 1981, the immunodeficiency disease AIDS was described and two years later, the disease -causing HIV virus was at the Pasteur Institute in Paris discovered that the best-studied virus is now more than ever. However, AIDS is still no cure and has become a pandemic.

Classification

The genus Lentivirus is divided into five different sub-groups, which are named after the hosts they infect: bovine, equine, ovine / caprine, feline lentiviruses and the lentiviruses of primates. These include, for example, the following species:

• Bovine immunodeficiency virus (BIV ) of cattle
• Jembrana disease virus in cattle

• Virus of equine infectious anemia ( EIAV ) Equidae ( horses, donkeys )

• Feline immunodeficiency virus (FIV ) of the House and big cats

• Maedi - visna virus ( MVV ) of sheep
• Caprine arthritis- encephalitis virus ( CAEV ) of goats

• Human immunodeficiency virus (HIV ) with the two types of HIV-1 and HIV-2
• Simian immunodeficiency virus (SIV) in different monkeys with various forms of

EIAV Jembrana and belong to the lentivirus, but they can also give rise to an acute disease in contrast to most other lentiviruses.

Differences from other retroviruses and evolutionary development

Lentiviruses differ from other retroviruses by a characteristic feature: they can, in contrast to, for example, alpha or gamma retroviruses affect the regulation of their own genes. For this reason, they are counted among the complex retroviruses. They are extremely variable in their nucleotide sequence. By the absence of an error correcting mechanism, and the Einsträngigkeit of the RNA genome, they have the fastest evolving with genomes.

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

Construction

Main article: Retroviruses # Design

Lentiviruses are among the complex retroviruses. You are enveloped and have a diameter of 80-100 nm, and they have like all retroviruses in their genome three " major genes ", gag, pol, and env that code for the viral proteins and in all lentiviruses in the order 5'- gag -pol - env - 3 are arranged '. They also have several additional genes, also called accessory genes (English accessory or auxiliary) are known and may be different from lentivirus to lentivirus. These genes and their products involved in the regulation, synthesis and processing of viral RNA and act partly contrary to the defense mechanisms of the host cells. HIV -1 contains, for example, the accessory genes vif, vpr, vpu, tat, rev, and nef. The long terminal repeat region (LTR ) region of lentiviruses is about 600 nucleotides ( nt) long, of which the U3 region of about 450 nt, the R region 100 and the U5 region 70 nt. By the accessory genes in the genome of the lentiviral -section is slightly larger than that of the simple retroviruses.

Among the trans-activators that increase the efficiency of transcription of the LTR promoter, are indeed, Tax and Tas. Rev and Rex are trans-activators that act post-transcriptionally.

Nef

Nef negative factor is a myristylated intracellular protein, which ensures that the CD4 receptor is down-regulated and no longer appears on the cell surface.

Rev

Rev ( regulator of expression of virion proteins) encodes a 13-19 kDa protein present in tetramers or larger aggregates. It accumulates in the nucleus and binds to RRE, the rev - responsive element in the viral mRNA, which these RNAs are preferentially exported from the nucleus and processed, resulting in increased expression efficiency.

Tas

TAS transactivator of spumaviruses, also named LOAD1 is a nucleäres protein binding in human spumaviruses to the BRE element to the U3 region of human spumaviruses.

Deed

Tat ( trans- activator of transcription ) coding for the Tat proteins that are produced during the replication cycle as the first viral proteins. They have the function to strengthen the HIV virus transcription efficiency. Indeed binds to the trans- activation- responsive region (TAR), which is found at the 5 ' end of the viral transcripts and provides improved elongation. Indeed, thus a RNA -binding protein, the TAR region, the first RNA enhancer element has been described. Tat proteins are activated by an acetyltransferase which transfers to acetyl on lysyl residues of the protein.

Vif

Vif (viral infectivity factor ) encoding the Vif protein, which binds to the RNA packaged in virus particles. 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 coding 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 viral particles by binding to the Gag polyprotein. In the course of the infection Vpr has various functions such as an effect on the accuracy of the reverse transcription, the import of the pre-integration complex in the nucleus, the progression of the cell cycle, regulation of apoptosis, as well as to the trans-activation of HIV - LTR, and various host genes.

Vpu

Vpu ( Viral protein u) was found in the genome of HIV-1 and SIV cpz of. It is 80-82 base pairs in length and has the function, in some human cell types to promote the release of virus particles. Vpu of HIV-1 group M ( major) accomplished this by a cellular viral defense mechanism, which is mediated by the protein tetherin suppressed.

Vpx

Vpx coding for the viral protein X ( Vpx ). It consists of 104-119 amino acids and has a molar mass of 12 to 16 kDa. The protein is packed into viral particles.

This gene is found only in the genome of the human lentivirus HIV -2 and SIV in primates of African green monkeys ( SIVagm ), the macaques ( SIVmac ), the Weißlid - mangabeys ( SIVsm ) and mandrills ( SIVdrill ). In the genome of HIV -1 or the chimpanzee SIV ( SIVcpz ), however, is vpx not exist. However, similar to the vpx vpr HIV -1 and SIVcpz and fulfills similar functions. vpx vpr is meerkats from incurred in a recombination event in the countryside.

Replication cycle

Main article: Life cycle of retroviruses

The replication cycle of lentiviruses runs as that of all retroviruses from, with the particularity that lentiviruses have the ability to overcome the nuclear envelope and thus also infect resting, not exploiting dividend in division of cells. The entry into the nucleus is performed after formation of the pre-integration complex (PIC) in the cytoplasm. Since the nuclear pores are smaller than the PIC, it must be an active transport process. In this process, both cellular and viral proteins are involved.

Biotechnological use

Lentiviruses are used in genetic engineering as viral vectors for targeted transport genes into target cells and to express it there.