Rabies Virus Research Paper

Rabies is a disease that is very much ignored and underrated in the western world. The threat of rabies is not a subject of discussion you hear every day, but it should be talked about in school or within the community to be competent when you find yourself in a situation associated with a wild animal. Public Health officials have been warning communities from Connecticut to Florida of ways to prevent exposure to the deadly virus, belonging to the family Rhabdoviridae. It is important to know about rabies because rabies always leads to death.

RSV belongs to the paramyxovirus family of viruses. The virion encompasses a helical nucleocapsid packaged in a lipoprotein envelope attained from the host cell plasma membrane during budding. The external surface of the envelope contains a periphery of surface spikes.

Viruses can replicate themselves but only within a host cell in which they hijack as they do not own any translational machinery, so it is unable to create new RNA or DNA fragments or create a new set of virions5. In the first stages of viral replication the virus will attach itself onto a host cell via the glycoprotein spikes which eject off the capsid – this is called adorption6. The virion will then transfer its genomic material whether its RNA or DNA into the host cell via penetration of plasma membranes and this occurs through receptors binding to receptor sites and activating a chain of reactions6,7. The virus will the inject its own genomic material into the host cell which causes the host cell to use its replication techniques to replicate the foreign genome meaning its expressed by the host cell – hijacking the cell6. The genomic material that is now in the cell will be replicated as the cell is infected and will express these new characteristics of the virus instead of being able to carry out its own job. The newly produced proteins and enzymes will now mature within the host cell and group together to form new virions and viruses. After these are fully matured the enzymes produced will catalyse the cell membrane of cells and allows the newly produced viruses to be released into the extracellular environment6. This process of replication is also the way in which viruses adapt to their environments another component of being classed ‘alive’ because they

Rabies is a zoonotic virus that causes around 55,000 deaths per year worldwide (WHO, 2014). While the disease is well-known and has been studied for many years, research is still being carried out to further try and understand the disease process. Primarily targeting the central nervous system, rabies will only begin to cause symptoms when it reaches the CNS, moving through the body via retrograde transport through nerves. There are two forms of the disease – furious rabies and paralytic rabies - occurring in 70% and 30% of cases respectively (WHO, 2014). The infection is usually fatal after the virus reaches the brain, with hosts having roughly five to seven days before death.

A virus is a capsule containing genetic material, even smaller than bacteria. The main task of virus is to reproduce. However, viruses need a suitable host to

Viruses are microscopic particles that invade and take over both eukaryotic and prokaryotic cells. They consist of two structures, which are the nucleic acid and capsid. The nucleic acid contains all genetic material in the form of DNA or RNA, and is enclosed in the capsid, which is the protein coating that helps the virus attach to and penetrate the host cell. In some cases, certain viruses have a membrane surrounding the capsid, called an envelope. This structure allows viruses to become more stealthy and protected. There are two cycles in which a virus can go into: lytic and lysogenic. The lytic cycle consists of the virus attaching to a cell, injecting its DNA, and creating more viruses, which proceed to destroy the host. On the other hand, the lysogenic cycle includes the virus attaching to the cell, injecting its DNA, which combines with the cell’s DNA in order for it to become provirus. Then, the provirus DNA may eventually switch to the lytic cycle and destroy the host.

The influenza virus usually has a round shape; it can be elongated or even have an irregular shape at times. In addition, it has a layer of spikes on its exterior. Note that there are two different types of these spikes. Each spike has its own protein, one is the hemagglutinin (HA) protein and the other is the neuraminidase (NA) protein. The HA protein lets the virus to attach to a cell, so it can enter into a host cell and start the infection process (every virus must enter cells in order to make more copies of themselves). The NA protein is needed for the virus to leave the host cell, so that new viruses that were made inside the host cell can infect more cells. Because these proteins are present on the surface of the virus, they are visible to the human immune system. Inside the layer of spikes, are eight pieces of RNA that contain the genetic information for making new copies of the virus. Each segment contains instructions to make one or more proteins of the virus.

Some viruses also have an outer bag of lipo-protein called an envelope. After a virus attaches to a living cell, it either enters the cell to release the genetic information, or, the virus injects the information through the cells outer lining. Thus changing the cells natural functions and forcing the cell to spend its energy to create copies of the virus. The cell will go on making copies of the virus until the cell is used up and dies. The virus then leaves the dead cell and invades a nearby cell and the process starts all over. There are five types of human herpes virus: Varicella zoster which causes chickenpox, Epstein Barr virus which causes infectious mononucleosis, cytomegalovirus which can cause cytomegalic inclusion disease in infants, and herpes simplex viruses 1 and 2.

The virus fuses with the cell’s plasma membrane. The capsid proteins are removed, releasing the viral proteins and RNA. Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. Reverse transcriptase catalyzes the synthesis of a second DNA strand complementary to the first. The double-stranded DNA is incorporated as a provirus into the cell’s DNA. Proviral genes are transcribed into RNA molecules, which serve as genomes for the next viral generation and as mRNAs for translation into viral proteins. The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). Vesicles transport the glycoproteins from the ER to the cell’s plasma membrane. Capsids are assembled around viral genomes and reverse transcriptase molecules. New viruses bud off from the host cell.

1) Ebola Virus- Belongs to the family Filoviridae. It has a single-stranded -sRNA genome, so it uses a RNA polymerase to create the +sRNA template, which acts as mRNA inside the host cell. The envelope is made up of peptidoglycan; the structure is made up of 7 structural proteins and 1 non-structural protein. This means it is an enveloped and susceptible to the outside environment. The Ebola virus replicates in Monocytes, Macrophages and Dendritic Cells. When the Ebola virus is ready to leave the host cell it buds out and takes part of the cell membrane with it. Ebola has an incubation period of 8-10 days. (CDC)

This little package of mayhem consists of relatively few parts. A virus is simply a protein capsule called a capsid, sometimes surrounded by an envelope, containing a genome. The genome consists of nucleic acids arranged as DNA or less commonly, RNA. Dozens of variants of this fundamental arrangement exist with differences in the structure of the capsule and the arrangement of the genome. Small differences or changes in these components allow some viruses to continue to outmaneuver researchers, while millions of dollars are spent trying to understand and eliminate them.

material of some viruses. RNA molecules are like DNA. They have a long chain of

The SH (small hydrophobic) protein, matrix protein (M), and the M2 protein are envelope-associated proteins that are not involved in viral attachment or syncytium formation (3). Other proteins such as the nucleoprotein (N), phosphoprotein (P), and the large nucleoprotein (L) are in the nucleocapsid. NS-1 and NS-2 are non-structure protein that is only found in the infected cells but not present in virions (3).

Once tightly bound the virus is endocytosed via coated vesicles. The virus is transported into late endosomes which acidify their content and hence induce conformational rearrangement of HA exposing the fusiogenic peptide sequence. The loop region of the HA becomes a coiled coil that mediates membrane fusion. The release of viral genome into the cytoplasm also requires protons that are pumped from the acidic endosome into the virion interior via the matrix protein M2 that acts as a proton channel. Viral RNA dissociates from M1 and is then imported in an ATP-dependent manner into the nucleus for transcription and translation. In humans, the replication of the influenza virus is usually restricted to the airways epithelial cells due to the limited expression of a serine protease, produced by nonciliated bronchial epithelial cells and which cleaves the HA precursor in HA1 and HA2 polypeptides, rendering the virions infectious. Replication and virions production occurs within hours after virus entry. The viral ribonucleoprotein (vRNP) complexes are released from the endosomes into the cytoplasm and subsequently transported to the nucleus, where replication and transcription take

Step 1: How will you identify the “vital” cellular protein that the virus targets for degradation? (Hint: think proteomics). (3 pts.)