Visna Maedi virus (VMV) belongs to the small ruminant lentivirus group (SRLV). In general, SRLVs enter the cell through the interaction of their glycosylated envelope protein with a cellular receptor on the cell's plasma membrane facilitating fusion of the viral and cellular membrane.[12] However, the specific cellular receptor that VMV binds is not entirely certain. A few studies have proposed MHC class II, CD4 and CXCR4 proteins as possible receptors however, none of these proteins have been established as the main receptor.[13][14] Another study suggests that C-type lectins part of the mannose receptor (MR) family play a role as an alternative SRLV receptor.[15] The mannose receptor is a 180-kDa transmembrane protein with eight tandem C-type lectin carbohydrate recognition domains (CRD) of which CRD4 and CRD5 are essential in recognizing mannose, fucose and N-acetyl glucosamine residues. Studies suggest that VMV gains entrance to the cell via mannosylated residues on its envelope proteins.[15] MR is involved in recognizing the surface of pathogens and is involved in phago- and endocytosis and mediating antigen processing and presentation in a variety of cells including monocyte/macrophages and endothelial cells.[16][17]
ReplicationHorizontal transmission[edit]
Horizontal transmission plays an important role among livestock due to their often close quarters, especially during winter stabling. Free virus or virus infected cells are generally transferred in through inhalation of respiratory secretions. Additionally, fecal-oral transmission often occurs through contamination of drinking water.[20] Sexual transmission has also been shown to be possible.[21] No link has yet been made between transmission and other excretory products such as saliva and urine.[20]
Vertical transmission[edit]
In endemically infected flocks of livestock, free virus and virus infected cells are passed through from mothers to lambs via colostrum and milk.[22] This is one of the key features in affected populations, as it contributes greatly to the virus becoming endemic in the flock.[23] Lambs are extremely vulnerable to infection due to the permeability of the guts of newborns [24]
Model system for HIV infection[edit]
Though it does not produce severe immunodeficiency, visna shares many characteristics with human immunodeficiency virus, including the establishment of persistent infection with chronic active lymphoproliferation;[2] however, visna virus does not infect T-lymphocytes.[7] The relationship of visna and HIV as lentiviruses was first published in 1985 by visna researcher Janice E. Clements and colleagues in the HIV field.[38]It has been postulated that the effects of maedi-visna infection in sheep are the "equivalent" of central nervous system disease and wasting syndrome found in human AIDS patients.[1][39] Despite limited sequence homologywith HIV,[1] the genomic organization of visna is very similar, allowing visna infection to be used as an in vivo[40]and in vitro model system for HIV infection.[41][42][43]
Research using visna was important in the identification and characterization of HIV. Nucleotide sequence analysis demonstrated that the AIDS virus was a retrovirus related to visna and provided early clues as to the mechanism of HIV infection.[9]
The viral tat gene encodes a 94-amino acid protein. Tat is the most enigmatic of the proteins of the visna virus. Most studies have indicated that Tat is a transcription factor necessary for viral transcription from the LTRs. Tat contains both a suppressor domain and a powerful acidic activator domain on the N-terminus.[32] It has been suggested that Tat interacts with the cellular AP-1 transcription factors Fos and Jun to bind to the TATA-binding protein and activate transcription.[29] However, other studies have suggested that the visna virus "Tat" protein is not a trans-activator for transcription but instead exhibits a function involved in cell cycle arrest, making it more closely related to the HIV-1 Vpr protein than Tat.[33]
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