Expression of factors associated to programmed cell death related to BoHV 5 propagation in vitro.

Abstract

The Bovine herpesvirus type 5 (BoHV-5), family Herpesviridae, subfamily Alphaherpesvirinae, belongs to the genus Varicellovirus. This virus is able to replicate in different tissues such as neural tissue, glandular, lymphoid and parenchymal organs and can remain in a latent state and lodge in the nerve ganglia, reactivated in stressful situations. Initially considered subtype BoVH-1, bovine herpesvirus type 5 (BoHV-5) is the causative agent of nonsuppurative meningoencephalitis usually fatal that affects mainly young cattle. This disease is highly prevalent in South American countries, and in Brazil, clinical cases of encephalitis by BoHV-5 were the second leading cause of encephalitis with undetermined etiology. The laboratory diagnosis direct detection of the etiologic agent, involves virus isolation in cell culture and electron microscopy. Viral isolation can be performed on MDBK cells (Madin Darby bovine kidney) cells, primary cultures of calf testis (TT), bovine fetal lung cells and bovine turbinate (BT). Programmed cell death (MCP) is a process that occurs in multicellular organisms for discarding cells and plays an important role during the inflammatory response and viral infection. The apoptosis, a type of MCP, is characterized by events such as reduction of cell volume, chromatin the condensate, with the disintegration of the core and the presence of vesicles called "apoptotic bodies". The activation of apoptosis can be initiated in two ways; by the extrinsic pathway (cytoplasmic) for cell surface receptors, through which specific ligands such as Fas, CD95 or Apo-1 and TNF (tumor necrosis factor receptor). This stimulation leads to recruitment and activation of proteolytic pro-caspase 8, activating caspase 3, 6 and 7 that culminates in apoptosis. Another way is the intrinsic one(mitochondrial), which involves the activation of a pro-apoptotic member of the Bcl-2 family, such as Bax and Bak. In response to the apoptotic stimulus, these ones are activated and increase the permeability of the outer mitochondrial membrane, leading to release of cytochrome c into the cytosol, this is associated with Apaf-1 and pro-caspase 9, wherein subsequent caspases are activated, leading in apoptosis. Besides its fundamental role in the control of apoptosis during infection, other functions have been attributed to mitochondria, mainly related signaling for the innate immune response during viral infection. In previous studies, indications of their involvement also in the innate immune response, specifically the signaling pattern recognition receptors (RRP) have been demonstrated. Mitochondria also crucially involved in viral infection with regard to energy production and oxidative metabolism. Changes in oxygen levels are detected and reported by mitochondria the cell through the production of reactive oxygen species (ROS). With regard to infection by BoHV-5, in a study with cell culture derived mesenchymal jelly Whatorn cord bovine, infection with this virus led to a regulation of the mitochondrial respiratory chain, keeping in this basal level even after the addition of stimuli, such as respiratory substrates. Recently demonstrated that the experimental infection of oocytes, sperm and embryonic with BoHV-5 does not interfere with embryo quality or development in vitro. Thus, it is possible to infer that the BoHV-5 has unknown mechanisms to inhibit cell death and prevent the host immune system.