Neurotropic Virus

Neurotropic Virus Ning RintiswatiFac. Of Med, GMU

Viral infections of the central nervous system or neurotropic viruses are often lethal. These diseases range from polio and measles, to rabies, Varicella-zoster, Herpes, West Nile, Japanese encephalitis, and AIDS. Such infections have profound public health consequences, and the understanding of these diseases involves understanding the interaction between the nervous system and the immune system.

Left: Picture of poliovirus. The poliovirus is extremely small, about 50 nm (nanometer = one-billionth of a meter) Courtesy of David Belnap and James Hogle

Cross-section of the poliovirus showing the RNA, capsid, and nerve cell receptors Illustration courtesy of Link Studio Polio virus

GLOBAL STATUS 2004

Polio virus:

the causative agent of poliomyelitis, is a human enterovirusmember of the family of Picornaviridae.Poliovirus is composed of a RNA genome and a protein capsid. The genome is single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is about 300 ngstrm in diameter with icosahedral symmetr y.

Pathophysiology

Poliovirus enters the body through the mouth, infecting the first cells it comes in contact withthe pharynx (throat) and intestinal mucosa. It gains entry by binding to an immunoglobulin-like receptor, known as the poliovirus receptor or CD155, on the cell membrane . The virus then hijacks the host cell's own machinery, and begins to replicate.

Phatophysiology

Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the tonsils (specifically the follicular dendritic cells residing within the tonsilar germinal centers), the intestinal lymphoid tissue including the M cells of Peyer's patches, and the deep cervical and mesenteric lymph nodes, where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream.

Pathogenesis and pathologyEnter through MouthMultiplies in Oropharynx tonsils and Intestines Excreted in Stool. Enters the CNS from Blood. Spread along the Axons of peripheral nerves to CNS. Progress along the fibers of the lower motor neurons spinal cord or brain.

Properties of Polio virus:Polio virus is entero virusContains 4 viral protein VP1 to VP 4 VP1 Carries the major antigenic site, and combines with type specific neutralizing antibodies

Inactivated at 55 0 c for 30 mt. Chlorine at 0.1 ppm Ether is not effective. Animal susceptibility. Monkey brain Requires Primate specific membranes. Contains 3 Antigenic types 1,2,3 Can be differentiated by ELISA and CF methods.

What is Poliomyelitis?polio= gray matter Myelitis= inflammation of the spinal cord This disease result in the destruction of motor neurons caused by the poliovirus. Polio is causes by a virus that attacks the nerve cells of the brain & spinal cord although not all infections result in sever injuries and paralysis. How is polio transmitted? Poliovirus is transmitted through both oral and fecal routes with implantation and replication occurring in either the orapgaryngeal and or in the intestine of mucosa. Polio cases are most infected for 7-10 days before and after clinical symptoms begin.

Polio infection Incubation 3 21 days On average 14 days Predisposing factors. Severe muscular acitivity can lead to paralysis, as it increases the blood flow May produce paralysis in the limb or bulbar region Injecting vaccines with adjuvant can predispose to paralysis Patients who underwent tonsillectomy have higher incidence as Ig G secretion is reduced Rarely oral Polio vaccine produces poliomyelitis.

RABIES Virus

Rabies virus belongs to the family: Rhabdoviridae.They can infect a variety of animals and plantsit is estimated that approximately 55 000 persons die of rabies each year in the world.

Rhabdovirusare negative strand RNA viruses; that is they have a single strand of RNA that is anti-sense to the messenger RNA needed to code for viral proteins. This means that the RNA cannot code directly for protein synthesis and must be copied to positive strand mRNA. As a result, the virus must carry its own RNA-dependent RNA polymerase.are rod shaped. Each virus particle is up to 100nm diameter and 400 nm long but this is very variable. They have an envelope derived from the host cell plasma membrane. The virus has only five proteins.

Herpes virus

Herpes simplex viruses (HSV)belong to the subfamily of Alphaherpesvirinae. Herpes viruses consists of a relatively large linear DNA genome of double-stranded DNA 150 kb in length, encased within an icosahedral capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument. The genome of Herpes viruses encodes some 100-200 genes. These genes encode a variety of proteins involved in forming the capsid, tegument and envelope of the virus as well as controlling the replication and infectivity of the virus.

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two species of the herpes virus family, which cause infections in humans An infection by a HSV is marked by watery blisters in the skin or mucous membranes of the mouth, lips or genitals.

Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus, with receptors on the surface of the host cell. initial interactions occur when a viral envelope glycoprotein called glycoprotein C (gC) binds to a cell surface particle called heparan sulfate. A second glycoprotein, glycoprotein D (gD), binds specifically to a receptor called the Herpes virus entry mediator receptor (HVEM) and provides a strong, fixed attachment to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex.

Following infection of a cell, herpes virus proteins, called immediate-early, early, and late, are produced. The early proteins transcribed are used in the regulation of genetic replication of the virus. On entering the cell, an -TIF protein joins the viral particle and aids in immediate-early transcription. The virion host shutoff protein (VHS or UL41) is very important to viral replication. This enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins. The viral genome immediately travels to the nucleus but the VHS protein remains in the cytoplasm.The late proteins are used in to form the capsid and the receptors on the surface of the virus. Packaging of the viral particles - including the genome, core and the capsid - occurs in the nucleus of the cell

concatemers of the viral genome are separated by cleavage and are placed into pre-formed capsids. HSV-1 undergoes a process of primary and secondary envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear membrane releasing a naked capsid into the cytoplasm. The virus acquires its final envelope by budding into cytoplasmic vesicles.

HSV may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia.During latent infection of a cell, HSV express Latency Associated Transcript (LAT) RNA. LAT is known to regulate the host cell genome and interferes with natural cell death mechanisms. By maintaining the host cells, LAT expression preserves a reservoir of the virus, which allows later recurrences to produce further infections.

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Japanese EnchephalitisThe causative agent JEP is an enveloped virus of the genus flavivirus and is closely related to the West Nile virus and St Louis enchephalitis virus. The positive sense single stranded RNA genome is packaged in the capsid which is formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The genome also encodes several nonstructural proteins also (NS1,NS2a,NS2b,NS3,N4a,NS4b,NS5). Japanese Encephalitis is diagnosed by detection of antibodies in serum and CSF (cerebrospinal fluid) by IgM capture ELISAViral antigen can also be shown in tissues by indirect fluorescent antibody staining.Over 60 complete genomes of this virus have been sequenced as of 2010.

Japanese encephalitis has an incubation period of 5 to 15 days and the vast majority of infections are asymptomatic: only 1 in 250 infections develop into encephalitis.Severe rigors mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptom of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions and a raised body temperature between 38 and 41 degrees Celsius. Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children. Transplacental spread has been noted. Life-long neurological defects such as deafness, emotional lability and hemiparesis may occur in those who have had central nervous system involvement. In known cases some effects also include nausea, headache, fever, vomiting and sometimes swelling of the testicles.

HIV virus

roughly spherical particles (sometimes called virions). The surface of each particle is studded with lots of little spikes. An HIV particle is around 100-150 billionths of a metre in diameter surround with a coat of fatty material known as the viral envelopeProjecting from this are around 72 little spikes, which are formed from the proteins gp120 and gp41. Just below the viral envelope is a layer called the matrix, which is made from the protein p17.

Assembly, Budding and Maturation Among the strands of messenger RNA produced by the cell are complete copies of HIV genetic material. These gather together with newly made HIV proteins and enzymes to form new viral particles, which are then released from the cell. The enzyme protease plays a vital role at this stage of the HIV life cycle by chopping up long strands of protein into smaller pieces, which are used to construct mature viral cores. The newly matured HIV particles are ready to infect another cell and begin the replication process all over again. In this way the virus quickly spreads through the human body. And once a person is infected, they can pass HIV on to others in their bodily fluids.

Creutzfeldt-Jakob disease (CJD)is a rare, degenerativeinvariably fatal brain disorder. onset of symptoms occurs about age 60, and about 90 percent of individuals die within 1 year. In the early stages of disease, people may have failing memory, behavioral changes, lack of coordination and visual disturbances. As the illness progresses, mental deterioration becomes pronounced and involuntary movements, blindness, weakness of extremities, and coma may occur.

In sporadic CJD, the disease appears even though the person has no known risk factors for the disease. This is by far the most common type of CJD and accounts for at least 85 percent of cases.

In hereditary CJD, the person has a family history of the disease and/or tests positive for a genetic mutation associated with CJD. About 5 to 10 percent of cases of CJD in the United States are hereditary.

In acquired CJD, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures. There is no evidence that CJD is contagious through casual contact with a CJD patient. Since CJD was first described in 1920, fewer than 1 percent of cases have been acquired CJD.

CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges under a microscope. CJD is the most common of the known human Kuru was identified in people of an isolated tribe in Papua New Guinea and has now almost disappeared. These include bovine spongiform encephalopathy (BSE), which is found in cows and is often referred to as mad cow disease; scrapie, which affects sheep and goats; mink encephalopathy; and feline encephalopathy. Similar diseases have occurred in elk, deer, and exotic zoo animals.

PrionsPrions propagate by transmitting a misfolded protein state. When a prion enters a healthy organism, it induces existing, properly-folded proteins to convert into the disease-associated, prion form; the prion acts as a template to guide the misfolding of more protein into prion form. prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicating when breakage causes two growing ends to become four growing ends