Transcript HSV-1
HSV-1 Biological properties 1.Morphology and structure 1>120-200 nm spherical icosahedral 2>core dsDNA linear (L segment and S segment ) 3>capsid 162 capsomeres HSV-1 -capsid from 400kV Spot-scan Electron Cryomicroscopy 4>envelope spike-like glycoproteins such as gB gC gD gE gG gH gI gL gM CULTURE HSV can replication in many cells Such as kidney of rabit, lung of human embryo. Cells infection by hsv become larger, round,and has inclusion body in neucleus (CPE) PATHOGENESIS HSV-1 Ocular HSV-1 Facial HSV-1 acute herpetic gingivostomatitis HSV Whitlow HSV-1 Ear Process 1. Attachment gC and/or gB attach to heparan sulfate proteoglycan (HS) on the cell surface Herpes Simplex Virus-1 on a blood lymphocyte 2.Penetration 1) gD interact with cellular receptors 2) gC, gB, gD, with gH, and gL trigger fusion of the viral envelope (nuclear) and the host cell plasma membrane a pH-independent 3Retrograde Axonal Capsid Transport 1 )HSV capsid undergoes rapid transport by retrograde axonal flow to the neuronal nucleus 2 ) the capsid fuses with the nuclear membrane and the dsDNA from the virion is injected into the nucleus via nuclear pores 4 Packaging empty capsid binds to an initiation sequence dsDNA is packaged into the empty capsid 5 Viron Budding viral capsids are enveloped at the nuclear membrane transport vesicles are transported through the cytoplasm of the infecte cell(anterograde transport) transport vesicles fuse with the plasma membrane, releasing virions to the extracellular space Attachment Penetration Retrograde Axonal Capsid Transport Viral Production Latency Viron Budding Recurrences TYPES OF INFECTION Primary infection Latent infection Recurrent infection Congenital and neonate infection MECHANISM Primary infection A key factor involved in the intracellular edema is the keratinocytes of the middle and basal layers which are infected and undergo cytolysis, resulting in the formation of an intraepidermal lesion，which rapidly evolves into an epidermal lesion, filled with yellowish fluid, causing displacement of chromatin Secondary infection gains access to the distal axonal terminae of sensory nerves and travels by retrograde axonal transport to neuronal cell bodies in sensory ganglia, usually the trigeminal ganglia, where further replication or latency can occur Trigeminal Nerve Recurrences can be triggered by numerous environmental stimuli including a common cold, fever, severe sunburn, physical fatigue, emotional disturbance, trauma, gastrointestinal disturbances, menstruation, pregnancy, debilitating illnesses, or food allergy Immune response in primary infections antibodies to HSV antigens can be detected within 4 - 8 days (IgM IgG IgA) viral antigens are presented on dendritic cells and macrophages to CD4+ Th1 cells lysis of the Infected cells ----CD4+ T-cells, CD8 + T-cells, NK cells Secondary IR HSV antigen is taken up by Lagerhan's cells and presented on MHC II to memory CD4+ Th cells The anti-viral functions of T-cells include cytotoxicity, inhibition of viral growth, lymphokine secretion, and support of CD8+ and humoral responses DIAGNOSIS Isolation and identification of virus Rapid diagnosis electroscope test detect HSV antigen detect DNA -----PCR TRETMENT Drug Mode of Action Administered Form Acyclovir Disrupts the virusí ability to reproduce. (replicate) Capsules or Tablets. Cream for use in oral herpes Primary--> for 10 days Recurrent-> for 5 days Valacyclovir Disrupts the virusí ability to Capsules or Tablets Primary--> w/in 48 hours --> for 10 days Recurrent -> w/in 24 hours -> for 5 days Famciclovir Disrupts the virusí ability to reproduce. (replicate reproduce. (replicate Capsules or Tablets. Cream for use in oral herpes Primary --> w/in 6 hours --> for 5 days VACCINE inactivated virus preparations treated with formalin Adjuvanted subunit Vaccine Skinner Vaccine