13 Genome structure Linear double-stranded DNA 120 - 230 kb Genetic complexity -- isomers
14 Genome structure Linear double-stranded DNA 120 - 230 kb Genetic complexity# of genes
15 Replication Penetration by fusion with plasma membrane Nuclear site of replication80 or so viral proteins are expressed in regulated fashion:IE - immediate earlyE - EarlyL - LateCapsids assemble in nucleus and bud through nuclear membrame
20 Three manifestations of HSV latency Key Feature: there is a wide spectrum of clinical presentationsSome individuals (5 - 10%) have frequent clinical reactivationMost individuals reactivation is clinically asymptomaticIn ALL cases, virus is shed
21 Transmission of HSV-1 and HSV-2 Skin to skin contactThe virus does not penetrate intact skinMild abrasion or chapping of skin can allow infection
22 Tissue tropism of HSV-1 and HSV-2 Causes 95% of orofacial herpes (remainder caused by HSV-2)Causes % of primary genital herpes (but seldom recurs there)HSV-2:Causes primary and recurrent genital herpes infectionsMay cause primary oral herpes but, like HSV-1 in genital area, it seldom recurs there
38 Asymptomatic Shedding of HSV Occurs in both HSV-1 and HSV-2The only form of shedding in 1/2 to 2/3 of infected patientsInvolves low amounts of virusAccounts for most transmissions to infected contacts and neonatesIs not completely suppressed by acyclovir
40 2/3of the acquisitions of genital herpes come from clinically asymptomatic partners
41 Alpha Herpesviruses Site of Latency Herpes Simplex Virus type 1 Sensory neuronsHerpes Simplex Virus type 2 Sensory neuronsVaricella Zoster Virus Sensory neuronsBeta HerpesvirusesCytomegalovirus LymphocytesHuman Herpesvirus 6 CD4 T cellsHuman Herpesvirus 7 CD4 T cellsGamma HerpesvirusesEpstein-Barr Virus B lymphocytesHuman Herpesvirus 8 Sarcoma tissue
42 Two Unique Features of VZV: Airborne spread or skin to skin contactMore severe infection if primary infection occurs as an adult
43 Complications of Varicella Reye’s SyndromeBacterial Superinfection of lesions (more common in younger patients)Varicella pneumoniaNeonatal varicella -- disseminated, 30% mortality
44 Varicella Pneumonia Age Fatalities per 100,000 <1 6.23 1 - 14 0.75 <
45 Varicella patients at risk ADULTSPREGNANCY (3rd trimester)IMMUNOCOMPROMISEDThe mortality rate for varicella pneumonia in leukemic children receiving chemotherapy is 1,000 times higher than in healthy children.Note: Children with isolated agammaglobulinemia are not at risk!
52 Varicella Vaccine Prevents 40 - 70% of chickenpox occurrence Greatly reduces the severity in the restAttenuated virusCan still establish latency and reactivateQuestion: How long will immunity last?
53 Complications of Zoster Postherpetic NeuraligiaAffects % of zoster patients over 50Pain may persist for months or even years
54 Alpha Herpesviruses Site of Latency Herpes Simplex Virus type 1 Sensory neuronsHerpes Simplex Virus type 2 Sensory neuronsVaricella Zoster Virus Sensory neuronsBeta HerpesvirusesCytomegalovirus LymphocytesHuman Herpesvirus 6 CD4 T cellsHuman Herpesvirus 7 CD4 T cellsGamma HerpesvirusesEpstein-Barr Virus B lymphocytesHuman Herpesvirus 8 Sarcoma tissue
55 Transmission of CMV In utero Early childhood (saliva, etc.) Venereal in young adultsBlood transfusionOrgan transplantation
56 Clinical Manifestations of CMV Normal Host:Asymptomatic in the majority of casesInfectious mononucleosisCongenital CMV:Primary CMV infection in 3rd trimester of pregnancy of a seronegative motherImmunocompromised:Pneumonitis in bone marrow transplantsRetinitis in AIDS patients
65 Heterophile Antibody (IM) EBV induces many cellular proteinsAn antibody against one of these new celular proteins is able to agglutinate sheep red blood cellsEBV monucleosis is heterophile antibody positiveCMV mono is heterophile antibody negative
66 IM Serology VCA IgM rises and falls early in infection VCA IgG antibodies persistEBV mononucleosis is heterophile antibody positiveCMV mononucleosis is heterophile antibody negative; no antibodies to VCA of EBV
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