Transcript Herpesviruses

D- virology
Herpesviruses
Herpes simplex I & II (cold sores, genital herpes)
Varicella zoster (chicken pox, shingles)
Cytomegalovirus (microcephaly, infectious mono)
Epstein-Barr virus (mononucleosis, Burkitt’s lymphoma)
Human herpesvirus 6 & 7 (Roseola)
Human herpesvirus 8 (Kaposi’s sarcoma)
Cold Sores
Zoster
Roseola
Human Herpesviruses
Virus
Subfamily
Disease
Site of Latency
Herpes Simplex Virus I
α
Orofacial lesions
Sensory Nerve Ganglia
Herpes Simplex Virus II
α
Genital lesions
Sensory Nerve Ganglia
Varicella Zoster Virus
α
Chicken Pox
Recurs as Shingles
Sensory Nerve Ganglia
Cytomegalovirus
β
Microcephaly/Mono
Lymphocytes
Human Herpesvirus 6
β
Roseola Infantum
CD4 T cells
Human Herpesvirus 7
β
Roseola Infantum
CD4T cells
Epstein-Barr Virus
γ
Infectious Mono
B lymphocytes, salivary
Human Herpesvirus 8
γ
Kaposi’s Sarcoma
Kaposi’s Sarcoma Tissue
Herpes Simplex Virus
Prototype of group
Virion stabiliy
• Enveloped virus
• Sensitive to dessication
• Easily inactivated by detergents and lipid
solvents
Virion structure
•Enveloped, spherical virion
•Icsoahedral capsid 120 - 200 nm
•>12 virally encoded
glycoproteins
•Tegument proteins
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
Life-long Latency
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
Eczema/Herpes
Herpes Simplex Virus type 2
•Infects the genital tract
•Is sexually transmitted
•Complicates childbirth
Diagnosis of Herpes Simplex Virus
Infections:
•Viral Culture
•Tzanck prep
•Culture with monoclonal antibody staining
•Serology
•Polymerase chain reaction (PCR)
Spectrum of HSV recurrence
•Asymptomatic shedding
•Shedding with clinically apparent
lesions
A study of HSV-2 recurrence in women
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
2/3
2/3
of the acquisitions of genital
herpes come from clinically
asymptomatic partners
Alpha Herpesviruses
Site of Latency
Herpes Simplex Virus type 1
Sensory neurons
Herpes Simplex Virus type 2
Sensory neurons
Varicella Zoster Virus
Sensory neurons
Beta Herpesviruses
Cytomegalovirus
Lymphocytes
Human Herpesvirus 6
CD4 T cells
Human Herpesvirus 7
CD4 T cells
Gamma Herpesviruses
Epstein-Barr Virus
B lymphocytes
Human Herpesvirus 8
Sarcoma tissue
Two Unique Features of VZV:
•Airborne spread or skin to skin contact
•More severe infection if primary infection occurs
as an adult
Complications of Varicella
•Reye’s Syndrome
•Bacterial Superinfection of lesions (more common in younger
patients)
•Varicella pneumonia
•Neonatal varicella -- disseminated, 30% mortality
Varicella Pneumonia
Age
Fatalities per 100,000
<1
6.23
1 - 14
0.75
15 - 19
2.70
30 - 49
25.20
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!
Neonatal Varicella
Zoster
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 Herpesviruses
Site of Latency
Herpes Simplex Virus type 1
Sensory neurons
Herpes Simplex Virus type 2
Sensory neurons
Varicella Zoster Virus
Sensory neurons
Beta Herpesviruses
Cytomegalovirus
Lymphocytes
Human Herpesvirus 6
CD4 T cells
Human Herpesvirus 7
CD4 T cells
Gamma Herpesviruses
Epstein-Barr Virus
B lymphocytes
Human Herpesvirus 8
Sarcoma tissue
Transmission of CMV
•In utero
•Early childhood (saliva, etc.)
•Venereal in young adults
•Blood transfusion
•Organ transplantation
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
Alpha Herpesviruses
Site of Latency
Herpes Simplex Virus type 1
Sensory neurons
Herpes Simplex Virus type 2
Sensory neurons
Varicella Zoster Virus
Sensory neurons
Beta Herpesviruses
Cytomegalovirus
Lymphocytes
Human Herpesvirus 6
CD4 T cells
Human Herpesvirus 7
CD4 T cells
Gamma Herpesviruses
Epstein-Barr Virus
B lymphocytes
Human Herpesvirus 8
Sarcoma tissue
EBV Mono
EBV mononucleosis
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
Antiviral therapy
Deoxyguanosine
Deoxyadenosine
Acyclovir
Ribavirin
Ganciclovir
Vidarabine