BIOL 6576 Exam # 3 Study Guide Lectures: 9-11Lecture 9 PolioPoliomyelitis, caused by the polio virus, is characterized by aseptic meningitis and a lytic infection of the anterior horn cells of the spinal cord.In the late 19th century, polio made a shift from being endemic to an epidemic disease in the US and Europe. Why? This is possibly due to a large mutation. It is more likely due to the development of closed sewer systems. Children were no longer naturally immunized by playing in the streets with feces and there was a loss of herd immunity.Poliovirus- Family picornaviridae, genus enterovirus- Small, linear +ssRNA, icosahedral capsid, naked- polyprotein cleaved into many proteins, replicate in cytoplasm in vesicles- transmitted via fecal-oral route and infects the intestines- 3 serotypes: each one causes different antibodies, each one causes paralytic - polioreceptor: PVR (poliovirus receptor) is part of the immunoglobulin family. It is normally expressed in muscle end plates and motor neurons. However, in people with acute poliomyelitis, muscle fibers express PVR. Pathogenesis of polio1. Polio is ingested and infects tonsils (oropharynx) and intestines. In the intestines, it infects the M cells of a tissue called Peyer’s patches. Very efficient replication occurs.2. Virus spreads to the lymphnodes and produces a minor viremia which infects organs andthe bone marrow. 90% of people clear the virus at this point. 3. The other 10%: this replication leads to a major viremia. Minor symptoms occur here (3-7 days). These symptoms include fever, headache, and sore throat. 4-8% of people clear the virus at this point in 1-2 days. 4. 1%: this major viremia goes into the CNS. Replication in the skeletal muscle allows viruses to move up the peripheral nerves to the spinal cord. Symptoms of the major illness include headache, vomiting, myalgia, and muscle weakness which occurs 9-12 days after infection. CSF pleocytosis occurs at the early stages of this major illness. 1/3 ofthis 1% yields nonparalytic polio with aseptic meningitis. This usually resolves itself in about 10 days.5. 2/3 of 1%: virus in the CNS causes necrotic lesions of the gray matter of the anterior horn of the spinal cord and the motor nuclei of the pons and medulla as well asinflammatory infiltrates. This leads to paralysis. The severity of the paralysis depends on the intensity of the lesions. a. 2 types of paralytic polio:i. spinal- weakness of skeletal muscles innervated by motor nerves ii. Bulbar: weakness of face, also problems with swallowing and respiration. These are innervated by cranial nerves.iii. Both types can happen at the same time in the same person.Prognosis- Most patients who experience paralysis can recover some mobility. 2/3 of patients retainsome motor deficits from minor weakness to major paralysis. Bulbar paralytic poliomyelitis causes significantly more deaths than spinal. This is because it prevents breathing due to paralysis of diaphragm muscles. Polio and guillian barre- GB has ascending paralysis and occurs symmetrically on both sides of the body. Polio is usually only on one side and not ascending.- GB has sensory abnormalities in 80% of cases. Polio doesn’t have them.- GB doesn’t exhibit CSF pleocytosis. Polio does.Vaccines2 early vaccines:- Brodie: killed-homogenized monkey spinal cord. Killed with formalin.- Kolmer: live attenuated-passed through mokey brain- These vaccines yielded little to no protection in monkeys or children. Monkeys that received the kolmer vaccine developed paralysis. Some children that had this vaccine developed poliomyelitis.Live vs killed- Live:o Adv: provides excellent immunity and no booster is neededo Disadv: difficult to prepare and less safe (can revert)- Killed:o Adv: quick to prepare and very safeo Disadv: the immunity doesn’t last a long time and boosters are needed.Current vaccines- Salk (IPV): killed-inactivated with formaldehyde. Uses the most virulent strains of all 3.- Sabin (OPV): live attenuated-passed through monkey brain, trivalent, oral, gives gut immunity (IgA), no reversion observed and no booster neededo Mutations in 5’ noncoding regions and/or capsid proteins- We currently use the salk vaccine.Polio has been eradicated in both Americas.Post-poliomyelitis20-30% of patients who recover from paralytic polio get this. This is a new onset of muscle weakness, atrophy, pain, and fatigue. 2 possible causes- Nerve fatigue: motor neurons are exhausted because of overworking during acute phaseand recovery- Direct infection or immunopathology: virus is still around in the body and it begins to replicate and infect againo IgG and IgM bands in CSF (IgM is for primary infection)o polio-like RNA in CSFLecture 10 ArbovirusesArboviruses (ARthropod BOrne viruses) are viruses transmitted by arthropods like mosquitos and ticks and can cause encephalitis.The 4 viral families containing arboviruses are togaviridae, flaviviridae, bunyaviridae, and reoviridae.- Family Togaviridae, genus alphavirus: western equine encephalitis, eastern equine encephalitis, and Venezuelan equine encephalitis- Family Flaviviridae, genus flavivirus: west nile virus, St Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, murray valley encephalitis virus- Family Bunyaviridae, genus Bunyavirus: LaCrosse virus (and other California viruses)- Family Reoviridae, genus Coltivirus: Colorado tick fever virusThese viruses have 3 different patterns of disease. 1. Fever, arthritis, and rash2. Hemorrhagic fever3. Neurologic diseases (encephalitis)Ecology of Arboviruses- The virus is transmitted within an enzootic cycle involving birds and rodents and mosquitos.- Humans get infected when we encroach on this natural cycle. - The species of mosquito that brings the virus to us is called the bridging vector.- Sometimes a mosquito can bring the virus to an animal to which we are closer to (usually a horse). This horse is called an intermediate invertebrate. This transmission is called an epizootic event. - We are dead end hosts, meaning the virus doesn’t get passed on from us to another animal or mosquito and it dies. This is somewhat because we usually have a low viremia in comparison to the vector which has a high and prolonged viremia.- Most human infection in asymptomatic or causes a minor illness. Only a few are major.- These viruses replicate both in the vector and the host in an extrinsic