Genome structure Linear double-stranded DNA 120 - 230 kb Genetic complexity -- isomers
Genome structure Linear double-stranded DNA 120 - 230 kb Genetic complexity # of genes
Replication Penetration by fusion with plasma membrane Nuclear site of replication 80 or so viral proteins are expressed in regulated fashion: IE - immediate early E - Early L - Late Capsids assemble in nucleus and bud through nuclear membrame
Three manifestations of HSV latency Key Feature: there is a wide spectrum of clinical presentations Some individuals (5 - 10%) have frequent clinical reactivation Most individuals reactivation is clinically asymptomatic In ALL cases, virus is shed
Transmission of HSV-1 and HSV-2 Skin to skin contact The virus does not penetrate intact skin Mild abrasion or chapping of skin can allow infection
Tissue tropism of HSV-1 and HSV-2 HSV-1: Causes 95% of orofacial herpes (remainder caused by HSV-2) Causes 10 - 30% of primary genital herpes (but seldom recurs there) HSV-2: Causes primary and recurrent genital herpes infections May cause primary oral herpes but, like HSV-1 in genital area, it seldom recurs there
Asymptomatic Shedding of HSV Occurs in both HSV-1 and HSV-2 The only form of shedding in 1/2 to 2/3 of infected patients Involves low amounts of virus Accounts for most transmissions to infected contacts and neonates Is not completely suppressed by acyclovir
Varicella patients at risk ADULTS PREGNANCY (3rd trimester) IMMUNOCOMPROMISED The 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!
Varicella Vaccine Prevents 40 - 70% of chickenpox occurrence Greatly reduces the severity in the rest Attenuated virus Can still establish latency and reactivate Question: How long will immunity last?
Complications of Zoster Postherpetic Neuraligia Affects 25 - 50% of zoster patients over 50 Pain may persist for months or even years
Alpha HerpesvirusesSite of Latency Herpes Simplex Virus type 1Sensory neurons Herpes Simplex Virus type 2Sensory neurons Varicella Zoster VirusSensory neurons Beta Herpesviruses CytomegalovirusLymphocytes Human Herpesvirus 6CD4 T cells Human Herpesvirus 7CD4 T cells Gamma Herpesviruses Epstein-Barr VirusB lymphocytes Human Herpesvirus 8Sarcoma tissue
In utero Early childhood (saliva, etc.) Venereal in young adults Blood transfusion Organ transplantation Transmission of CMV
Clinical Manifestations of CMV Normal Host: Asymptomatic in the majority of cases Infectious mononucleosis Congenital CMV: Primary CMV infection in 3rd trimester of pregnancy of a seronegative mother Immunocompromised: Pneumonitis in bone marrow transplants Retinitis in AIDS patients
Heterophile Antibody (IM) EBV induces many cellular proteins An antibody against one of these new celular proteins is able to agglutinate sheep red blood cells EBV monucleosis is heterophile antibody positive CMV mono is heterophile antibody negative
IM Serology VCA IgM rises and falls early in infection VCA IgG antibodies persist EBV mononucleosis is heterophile antibody positive CMV mononucleosis is heterophile antibody negative; no antibodies to VCA of EBV