BIOL 4576 Exam # 2 Study Guide Lectures: 5-8Lecture 5 (February ?) Viral Aseptic Meningitis- Aseptic meningitis: meningeal inflammation in which a common bacterial agent cannot be identified in the CSF. There’s no involvement of brain parenchyma (encephalitis) or spinal cord inflammation (myelitis). However it could be viral, fungal, or acid-fast bacteria. - No long-term sequelae (symptoms) and is a seasonal disease (summer).- It is commonly cause by enteroviruses, arboviruses, and HSV2. It is uncommonly caused by mumps, LCMV, and HIV. It is rarely caused by Flu A and B, parainfluenza, measles, B19, and HSV1. Enterovirus Meningitis- 2/3rds of culture negative CSF samples for aseptic meningitis are enteroviruses found by PCR.- Children are the primary victims.- Enteroviruseso Family picornaviridaeo Polio, coxsackievirus A and B, echoviruso Naked, icosahedral, +ssRNA, only 6-8 proteins from genome- Pathogenesiso Route of entry: fecal oral, rarely respiratoryo Viruses are stable in the acidity of stomach.o Virus moves through the stomach and goes into the lower GI tract. Primary infection occurs in enterocytes.o Viruses transverse through the cells of the intestinal lining and infects Peyer’s patches where significant replication occurs. o This causes minor viremia which infects liver, lungs, and heart. o Replication in these soft organs causes major viremia. This causes symptoms.o Invasion of the CNS can occur in either viremia but commonly in major viremia. This can happen by leakiness of blood vessels or by the direct infection of endothelial cells that upregulate enterovirus receptors.- Pathologyo Children Inflammation of choroid plexus in lateral and 4th ventricles. Fibrosis (scar tissue formation) of vasculature, ependymal lining, and basal leptomeninges. Moderate reduction in size of ventricles and increased number of astrocyteso Neonates They are at risk for severe systemic illness which meningitis is common. Higher chance of morbidity and mortality (10%), possibly due to transplacental infection Causes other major problems like hepatic necrosis, myocarditis, and necrotizing enterocolitis Death usually due to liver failure or myocarditiso Others Rarely severe or fatal Biphasic fever, vomiting, rash, diarrhea, nuchal rigidity (cant move neck well-50%), headache, photophobia CSF: nonspecific: pleocytosis, elevated protein and ICP Lasts about 1 weekMumps Meningitis- Paramyxoviridaeo Enveloped/pleomorphic, helical, -ssRNA, small genome (7 proteins), 1 serotype- Pathogenesiso Route of entry: respiratoryo 1st round of replication occurs in upper respiratory epitheliumo Virus infects parotid gland which causes parotitis (swelling and tissue damage)o Virus enters blood and infects kidney, gonads, placenta, pancreas, and heart. Thiscan cause sterility in older men.o Invasion of CNS occurs by infected mononuclear cells.- Pathologyo More common in males (2X) neurologic symptoms 3X more commono Meningitis can occur before parotitis (parotitis occurs in 50% of patients)o Nonspecific symptoms including fevero CSF: persistent pleocytosis, possible changes in protein and glucoseo Rapid and full recovery normalo Vaccine can cause meningitis but it is benign.Lymphocytic choriomeningitis virus- A specific infectious disease caused by a filterable virus- Arenaviridaeo Enveloped/pleomorphic, helical, -ssRNA segmented, nonfunctional ribosomes- Zoonotic: mice to human. Almost all cells of carrier mice are infected because they have developed an immune tolerance (recognize virus as self). They excrete virus inrespiratory droplets and feces. Winter months cause mice to move inside and there are more human cases. Hamsters can transmit it often. - Clinical presentation: symptoms in 15% of infectionso 1st symptoms are flulike with possible pneumonitis or they can present no symptoms.o There can be 2 phases. 1-flulike 2-headache, fever, stiff necko CSF symptoms nonspecifico Mild encephalitis is possibleo Symptoms can persist for over a montho Rarely fatal, rare neurologic complications, recovery usually completeHerpes Simplex 2- Benign and self limiting. No encephalitis. - 33% of women and 11% of men- Symptoms: headache, photophobia, nuchal rigidity, pleocytosis- Meningitis can occur at either primary infection or during a reactivation.- Neonates can die from this due to panencephalitis.Mollaret meningitis- Spontaneous recurrent fever and meningeal irritationo CSF pleocytosis happens each time.- Found to be HSV1 by PCR- Intrathecal: into CSFLecture 6 Herpes Simplex virus latency and encephalitis8 types of human herpes virus: grouped into α, beta, and gamma o Α: lesions/pox: short growth, rapid spread, latent in sensory neuronso B: mono, hepatitis, fetal problems, roseola: long growth, slow spread, latent in secretory glands, restricted hosto G: mono, Kaposi, burkitts: epithelial cells and lymphocytes, latent in lymphocytesBlood: cytomegalovirus, Epstein barr, 6, 7, 8neural: HSV 1, HSV 2, varicella-zoster (both)Herpesviridae- Enveloped, icosahedral, big, linear dsDNA- HSV1: 90 genes in 3 temporal classes: immediate early/α-gene activation, early/beta-DNA replication, late/gamma-capsid proteins- Cascade regulation: IE genes build up and turn on next round of E, etc…o Tegument proteins activate transcription and host shutoff- Envelope by budding off inner nuclear membraneLatency- 2 types: dynamic: virus persists with small amounts of continuous shedding of infectious virus static: persistence of viral genome and no production of infectious virus but canreactivate later and cause disease- Operational definition: o culture of ganglion homogenate: positive culture in 5 days means active infectiono culture of ganglion explant: positive culture in 5 days means active infection positive culture in 2-11 weeks means virus reactivation from latency- Viral genome conserved and the genome is kept in the nucleus but outside host chromosome in circular form and is associated with histones. There are also many copiesof the genome per neuron.- 25% of neurons latently infected and you can’t detect protein synthesis.- Only transcription that occurs is latency associated transcripts. o 2kb intron of RNA in a very stable lariat structure which is expressed due to a neuronal promoter and is also found during productive infectiono Unknown function- Stageso Primary infection of sensory ganglia, establishment of