A Review Of Rabies Virus Biology Essay

A Review Of foolishness Virus biology Essay Imagine a disorder which had no interposition choice once you felt its symptoms. Unless you had suspicion that you were potenti eithery infected, you would get misdiagnosed and you would die in isolation, restrained, and heavily drugged (3). Unfortunately such a disease is a reality. rabidity computer computer computer computer virus results in nearly 100% fatality if non treated, and is responsible for over 55,000 human terminals every year, which is possible a hidebound foretell due to under reporting and misdiagnosis (3). Rabies is ca apply by a Baltimore Class 5 virus in the order Mon whizzgavirales. Rabies virus is in genus Lyssavirus, and its species designation is Lyssavirus craziness (4). Rabies virus is pathologically feature film in its neuroinvasiveness and neurotropism, traveling up the nervous system from the contuse settle and into the brain where it causes severe neuropathology and death (1). This paper aims to explore the major(ip) components and mechanisms of Rabies virus, the disease cause by this virus, its treatments, and the public health impact of the disease. Rabies virus is characterized morphologically under an electron microscope by its weed shaped dimensions, thick studded with glycoprotein projections in the membrane. The virus itself is fairly simple, beingness composed of however five proteins and its single-stranded, antisense, ribonucleic acid genome 12 kb in length. The close valuable protein pathogenically is the glycoprotein encoded by the virus. This glycoprotein take shapes rough 400 trimeric projections on the surface of the envelope, and is a major contributor in the virus capability to spread cell-to-cell (1,4). The glycoprotein is to a fault highly antigenic and may be responsible for the triggering of apoptosis in neural tissue. The apoptotic cells ar thought to be very s starting timely unclutter from the CNS, and result in the necrosis of the tis sue in that ara (1). hyaloplasm protein is produced by Rabies virus and essentially holds the envelope containing glycoprotein to the core of the virus (3,4). It is also matrix protein that is responsible for bullet morphology of rabidness virus and its budding capability from host cells (4,3). The core of the virus is composed of the (-) ribonucleic acid genome bound by nucleoprotein which coils it into a helixed ribonucleoprotein core or RNPC. Phosphoprotein and polymerase associate with the RNPC and form the remainder of the virus core contained inside of the matrix protein capsid (4). Rabies virus has a similar life cycle to typical Baltimore secernate 5 enveloped viruses. Replication takes place in the cytoplasm, in specialized compartments cognise as Negri bodies. These areas were previously the almost emergenceive characteristic in name folly histologically. The cycle begins with the stick arounding of the virus envelope to the host cell, most likely through the gl ycoprotein trimers found on the surface. Rabies virus shows a cellular tropism for nerve cells, but can also utilize sinew cells. The virus enters the cell by pinocytosis. The virus then fuses with the endo approximately due to the diversity in pH and injects the RNPC into the cytoplasm. The RNA dependent RNA polymerase that the virus brought with it goes to hunt down, transcribing the antisense RNA into sense RNA for use by the host cells ribosomes. The viral polymerase attaches 5 caps and poly-adenylate tails to the RNA onwards translation into the five viral proteins. The glycoprotein make by the host ribosomes undergoes modification by the Golgi complex and endoplasmic reticulum before migrating to the plasma membrane of the cell. The concentration of nucleoprotein versus the concentration of leader RNA triggers the alter from protein business to genome payoff. Genome reproduction occurs in the same manner as sepa stray Baltimore class 5 viruses. The replicated (-) RNA genome is bound by nucleoprotein which creates the helixed ribonucleoprotein core, after which phosphoprotein and polymerase bind and complete the core of the virus. Matrix proteins then bind around the RNPC and forms the bullet shaped capsid. The M-RNPC then travels through the cytoplasm and buds from areas of the plasma membrane that abide high concentrations of glycoprotein. The complete rabies virus is then capable of contagion (4). Rabies is transmitted by an infected animals saliva getting into the tissues of a healthy mammal. Rabies is unable to penet prize intact skin, therefore most eccentric persons of infection occur detecting a bite or eat away from an infected animal (3). The virus enters the body through the wound and travels from the wound site to the brain by using the hosts nerves. Rabies virus is capable of this retrograde axonal transport because it can combine cell-to-cell spread and trans-synaptic spread, although we are unaware of how trans-synaptic spr ead is carried out (1). There is evidence that these methods of movement are made possible, and are controlled by, the glycoprotein that coats the Rabies virus membrane (1). The virus replicates within the nerves, slowly making its way to the brain and salivary glands at the rate of 15-100 mm per day (2). As the virus makes its way up the nerves, it causes no symptoms and is non transmissible through saliva. This period is known as the incubation period and can last from 3 weeks to 6 years (2,4). The rate of spread in the nervous system depends on the virus pulmonary tuberculosis rate by the nerve cells, the speed of axonal transport, the rate of replication, and the strains capacitor for trans-synaptic spread (1). Rabies virus typically has a low replication rate, and experimentally this has been seen to have an inverse relationship with pathogenicity, possibly due to the default of the immune system through low viral load. The low replication rate could also be beneficial t o pathogenicity by preserving the nerves used to travel into the CNS (1). Once in the CNS, the virus can follow the facial and glossopharyngeal cranial nerves to the salivary glands, which it infects and buds virus into the acinose lumen (5,4). The virus continues to travel up into the brainstem and brain where it causes the runner of the clinical symptoms. There are several theories as to how rabies virus conducts its neuropathogenesis, the first being that the virus shuts down host maintenance genes and reduces protein production in neural tissue. The second theory proposes that the virus interferes with serotonin cover song and release. The third theory is that glycoprotein pushes neurons into apoptotic pathways and the resulting dead cells do not get clean-cut from the CNS and cause necrosis of the surrounding cells. The remaining theories center on inactivation of voltage gated ion channels (1). The neuropathology of rabies results in quickly progressing and devastating sy mptoms. Upon experiencing the first clinical symptom, the individual typically has 1-7 days before death and has no chance of recovery. The first clinical symptom is neuropathic pain and tickling at the wound site after healing (4). This is caused by viral replication in the dorsal root ganglion of the afferent sensory nerve from the wound site causing action potential generation (2). The major clinical symptoms fever, headache, fatigue, anxiety, fervor, confusion, hallucinations, and insomnia are not unique to rabies and cannot be used as a diagnostic tool. These symptoms are likely caused by an agitation of the brain, spinal cord, and nerve roots (2,4). clinical progression usually follows one of two routes furious rabies in which there is extreme agitation and aggression, or dumb rabies in which there is early barrage paralysis and decreased activity (3). Both eventually lead to paralysis, coma, and the cloture of the respiratory system, resulting in death (3). The aggressio n caused by furious rabies as well as the heavily salivation, and saliva transmission all combine into a very legal transmission strategy for the virus (4). give-and-take of rabies virus infection must be make early and aggressively. Immune response to rabies virus is much lour than comparable diseases, which is surprising considering that glycoprotein is highly antigenic. In addition, compromised immunity had no effect on rabies pathogenesis, which means the pathology we see in healthy human beings is as bad as the disease can get (1). Treatment must be carried out before clinical symptoms set in, as the treatment only acts to stop the virus from r distributivelying the brain. Post-exposure protective treatment regimens consist of cell-cultured vaccine administration, and in dire cases, administration of immunoglobulin upriver of the wound to stop disease progression and also at the topical anaesthetic wound site to stop infiltration (3). Preventative treatment consists of a course of vaccines and the irrigation of potential infected wounds with a povidone-iodine solution (4). With early post-exposure prophylactic treatment, recovery is nearly 100%. However, if post-exposure prophylactic treatment is started after trespass of the CNS and presentation of clinical symptoms, treatment is usually ineffective (3). If clinical symptoms begin, treatment paradigms shift to a supportive role, usually consisting of isolation to embarrass transmission, overburdened sedation to avoid awareness and agitation, and IV morphine to assuage clinical symptoms (2). Rabies virus has caused disease on every unsullied except for Antarctica (3). The disease claims at least 55,000 human lives each year, with untold numbers of screwball animals. The heaviest disease burden is in developing countries in Africa and Asia, with these two continents accounting for 95% of the total deaths recorded each year. It is therefore apparent that rabies case numbers are capable of be ing sizably reduced, but a wish in infrastructure will eternally be the biggest obstacle. There are several factors to consider when questioning wherefore rabies is so prevalent in developing countries, the first of which is that rabies is under reported, and frequently misdiagnosed unless a post-mortem diagnosis is made, therefore the data concerning rabies health impact is lower than actual. The second cause of high rabies burden in developing countries is directly related to the last low estimates of the disease cause a lack, or disproportionate level, of support and wariness on a governmental level. The third cause is that rabies disease loads are not equally distributed across society. As we frequently see in disease of the developing origination, the rural poor are most likely to get infected and die from this disease. In the case of rabies, rural children from poor families are at highest risk of the disease not only due to their lack of education about rabies and lack of money for full treatment, but also because children are more likely to play with stray dogs, the main carrier of rabies from animals to humans and seen as the beginning in 30-60% of rabies cases in children under 15 years old. Animal workers are also very likely to be exposed, as are those who spend a significant amount of time outdoors, whether for work or leisure (2). While dogs are the most common source of rabies transmission to humans, the main reservoirs of the disease are unjustifiable animals. Raccoons, bats, wild foxes, skunks, and wolves are the largest reservoirs of disease and their transmission to dogs accounts for the resulting human infection. Therefore, the most represent effective rabies containment program is centered on dog vaccination, although it is still a heavy financial drain on society. The estimated cost in the joined States for rabies stripe and treatment each year is $300 trillion (2). However, cost depends on many factors including the character istics of post-exposure prophylactic treatment ( gingerroot). The cost for pep can vary depending on the vaccine used, the regimen of the vaccine administration, the lineament of immunoglobulin used, and the route by which all of this is administered. In Asia and Africa the estimated cost of PEP treatment yearlyly was $583 million. The bulk of the cost was incurred by Asia due to its heavy use of PEP treatment. On African and Asian continents the annual estimated cost of lost livestock due to rabies was $12.3 million, while a 1985 estimate by Latin American countries estimated their annual lost cattle at 100,000 head, with a total cost of $30 million per year. On the topical anesthetic level, a course of PEP is roughly $40 in Asia and $49 in Africa. While this may not seem like much, when annual income is only a few hundred dollars per year per person, the cost becomes roughly 30-50 days of work per adult. Many infected people do not want to go to the hospital for treatment due t o the amount of bemused work, and some of the more archaic vaccines still used in some developing countries can cause side effects lasting up to six months. However, even with the high cost treatment still saves tens-of-thousands of lives each year. The estimated number of deaths if PEP treatment was not used is approximately 330,000 in Asia and Africa (2). Rabies virus causes tremendous, fatal disease in the developing world and its presence is far too common for the level of effective prevention and treatment available. Rabies still claims over 55,000 lives each year, largely in developing countries in Africa and Asia. This simple Baltimore Class 5 virus packs quite an lethal punch in its ironically bullet shaped capsid, and shows fabulous tenacity in its host (4). Although it is unlikely due to the heavy wild animal reservoirs, ridding the world of this disease would be a tremendous remotion of burden from mankind and animals. References1) Dietzschold, Bernhard, Jianwei Li, M ilosz Faber, and Matthias Schnell. Concepts in the pathogenesis of rabies. Future virology. 3.5 (2008) 481-490. Print.2) join Nations. WHO Expert character reference on Rabies. Geneva World Health Organization, 2005. Web. 30 attest 2010.3) United Nations. Human and Animal Rabies. Geneva World Health Organization, 2010. Web. 31 March 2010. .4) United States. Rabies. Atlanta Centers for Disease Control and Prevention, 2010. Web. 31 March 2010. .5) Waxman, Stephen. Clinical Neuroanatomy. 25th ed. New York Lange Medical Books/McGraw-Hill, 2003. 113,119. Print.