BIOL 4576 Exam 2 Study Guide Lectures 5 8 Lecture 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 Enteroviruses o Family picornaviridae o Polio coxsackievirus A and B echovirus o Naked icosahedral ssRNA only 6 8 proteins from genome Pathogenesis o Route of entry fecal oral rarely respiratory o 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 Pathology o 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 astrocytes o 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 myocarditis o 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 week Mumps Meningitis Paramyxoviridae o Enveloped pleomorphic helical ssRNA small genome 7 proteins 1 serotype Pathogenesis o Route of entry respiratory o 1st round of replication occurs in upper respiratory epithelium o Virus infects parotid gland which causes parotitis swelling and tissue damage o Virus enters blood and infects kidney gonads placenta pancreas and heart This can cause sterility in older men o Invasion of CNS occurs by infected mononuclear cells Pathology o More common in males 2X neurologic symptoms 3X more common o Meningitis can occur before parotitis parotitis occurs in 50 of patients o Nonspecific symptoms including fever o CSF persistent pleocytosis possible changes in protein and glucose o Rapid and full recovery normal o Vaccine can cause meningitis but it is benign Lymphocytic choriomeningitis virus A specific infectious disease caused by a filterable virus Arenaviridae o 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 in respiratory 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 infections o 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 neck o CSF symptoms nonspecific o Mild encephalitis is possible o Symptoms can persist for over a month o Rarely fatal rare neurologic complications recovery usually complete Herpes 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 irritation o CSF pleocytosis happens each time Found to be HSV1 by PCR Intrathecal into CSF Lecture 6 Herpes Simplex virus latency and encephalitis 8 types of human herpes virus grouped into beta and gamma o lesions pox short growth rapid spread latent in sensory neurons o B mono hepatitis fetal problems roseola long growth slow spread latent in secretory glands restricted host o G mono Kaposi burkitts epithelial cells and lymphocytes latent in lymphocytes Blood cytomegalovirus Epstein barr 6 7 8 neural HSV 1 HSV 2 varicella zoster both Herpesviridae Enveloped icosahedral big linear dsDNA HSV1 90 genes in 3 temporal classes immediate early gene activation early betaDNA 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 membrane Latency 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 can reactivate later and cause disease Operational definition o culture of ganglion homogenate positive culture in 5 days means active infection o 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 copies of 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 infection o Unknown function Stages o Primary infection of sensory ganglia establishment of latency maintenance of latency reactivation from latency Reactivation can be triggered by local or systemic conditions not associated with destruction of neuron Role of immune system in establishment and maintenance of latency o Acute infection of ganglion CD8 T cells infiltrate ganglion 5 7