Herpesviruses

Important Characteristics
 Virion: Spheric (Icosahedral), d = 150 – 200 nm
 Genom: dsDNA, linear, 123 – 235 kbp, repeated sequences
 Proteins: > 35 proteins inside virion, synthesized in host nucleus
 Envelope: Contain viral glycoproteins, Fc receptor, originated from nuclear
membrane
 Replication: Nucleus, budding from nuclear membrane
 Etc:
 Codes many enzymes
 Causes latent infections, some causes cancer
 Reactivated by immunosuppression

Famili Virion Genome Nucleocapsid Virion MC (hrs)

replic. form. Maturation
Herpesviridae + N N M 15-72
Classifications
Divided into 3 Subfamilies:
 Alpha (α)
 HHV-1
 HHV-2
 HHV-3
 Beta (β)
 HHV-5
 HHV-6
 HHV-7
 Gamma (γ)
 HHV-4
 HHV-8
Aplhaherpesvirinae
Alphaherpesvirinae
 Consists of
 HHV-1  Herpes Simplex Virus type 1
 HHV-2  Herpes Simplex Virus type 2
 HHV-3  Varicella-Zoster Virus

 Known for its relatively short reproductive cycle,

targeting mainly epithelial cells, and causing latent
infections in neurons

 The most important herpesviruses in animal virology

Herpes Simplex Virus type 1 / HSV-1
 Cause
 Gingivostomatitis
 Pharyngotonsilitis
 Herpes labialis
 Keratoconjunctivitis
 Encephalitis (10-20%)
 Genital herpes (uncommon)
 Transmitted through direct
contact or oral secretions
 Glycoproteins
 gC  complement binding
protein (C3b)
 gD  enable entry to host
cell
 gE  Fc receptor, binds to
IgG Fc and inactivates
neutralizing agents
 gG  discriminate HSV-1
(gG-1) to HSV-2 (gG-1)
 Latent in trigeminal ganglia
(tendency, not absolute)
Herpes Simplex Virus type 2/ HSV -2
 Cause  Same glycoproteins as
 Meningitis HSV-1
 Genital herpes
 Neonatal herpes   Latent usually in sacral
congenital, mortality 65% root ganglia
 Oral herpes  uncommon

 Transmitted through
sexual contact and
perinatally (prev:
cesarean)
HSV-1 and HSV-2 Replication
 Infect cell, produce early, immediate-early, and late proteins
 Early proteins  used in regulation of genetic replication of the virus.
 α-TIF protein joins the viral particle and aids in immediate-
early transcription. Tegument shutoff protein (VHS or UL41) is very
important to viral replication. This enzyme shuts off protein synthesis
in the host, degrades host mRNA, helps in viral replication, and
regulates gene expression of viral proteins.
 The late proteins are used to form the capsid and the receptors on the
surface of the virus. Packaging of the viral particles — including the
genome core and the capsid - occurs in the nucleus of the cell. HSV-1
undergoes a process of primary and secondary envelopment. The
primary envelope is acquired by budding into the inner nuclear
membrane of the cell. This then fuses with the outer nuclear membrane
releasing a naked capsid into the cytoplasm. The virus acquires its
final envelope by budding into cytoplasmic vesicles.
Varicella-Zoster Virus / VZV
 Cause  Presentation in
 Varicella (Chickenpox) Immunocompromised
 Zoster (Shingles) patients
 Zoster multiplex
 Chickenpox  asynchronous  Zoster sine herpete
vesicle, occurs primarily on  Myelitis
trunks, lesions are superficial,  Keratitis
contagious before symptomps
appear
 Latent usually in dorsal
 Zoster  reactivation of VZV, root ganglia
increased occurance with age
and impaired immune function
Lab Diagnosis
 Cytopathology
 Rapid Giemsa stain (Tzank smear), shows multinulcleated giant
cells
 Cannot differentiate between HSV-1, HSV-2, and VZV
 Virus isolation and identification
 Immunofluorescent test  distinguish HSV-1 to HSV-2
 PCR
 Use CSF for HSV in CNS
 Serology
 Use of specific-type HSV antibody
Betaherpesvirinae
Betaherpesvirinae
 Consists of
 HHV-5  Cytomegalovirus (CMV)
 HHV-6  Roseolavirus
 HHV-7  Pityriasis Rosea

 Known for its long reproductive cycle, often causing

infected cells to become enlarged, and become latent in a
variety of tissues

 HHV-6 is divided into HHV-6A and HHV-6B, and

classified as distinct species in 2012
Cytomegalovirus / CMV
 Cause  Cytomegalic inclusion disease:
 Bone pain
 Heterophile-negative  Nausea and vomitting
mononucleosis  Jaundice
 Splenomegaly
syndrome  Thrombocytopenia
 Cytomegalic inclusion  Mental retardation
 Microcephaly
disease  Calcifications of CNS and kidney
 IC patients: pneumonia,
hepatitis, encephalitis,  Congenital CMV infection  Most
common cause of congenital
retinitis, neuropathy) abnormalities, most at risk of infection
during the 1st trimester

 HIV patients  CMV retinitis (20 –

30%)
Lab Diagnosis
 Virus isolation
 Translucent cells, enlarged with giant intranuclear inclusion 
Owl’s eye
 Slow, needs 2 – 3 weeks
 PCR
 Antigen Detection Test
 Monoclonal antibody against viral antigen
 Serology
 IgM for new infection, IgG for past infection
Owl’s eye inclusion bodies
HHV-6
 Disease: Roseola infantum /  Treatment: Symptomatic,
Exanthema Subitum / The Sixth
Disease (HHV-6B) use of Ganciclovir have
 Abrupt onset of high fever for 3 – 5 shown some success
days followed by erythematous
maculopapular rash that appears with
the return of normal temperature

 HHV-6A : more neurovirulent,

usually found in patients with
multiple sclerosis

 Cellular receptor : CD46

 Transmission: via saliva of parents,

90% seropositivity in older than 2
years children
Gammaherpesvirinae
Gammaherpesvirinae
 Consists of
 HHV-4  Epstein-Barr Virus (EBV)
 HHV-8  Kaposi’s Sarcoma-associated Herpesvirus (KSHV)

 Known for its variable reproductive cycle time, infects

and become latent in primarily lymphoid tissue
Epstein-Barr Virus / EBV
 Cause  EBV’s infectious
 Infectious Mononucleosis
mononucleosis is
 Associated with Ca
nasopharyngeal and Burkitt’s heterophile positive; it
lymphoma generates IgM and
 IC patients: hairy cell
agglutinate sheep and
leukoplakia
horse RBC
 Primarily infect and become latent in
B-cells
 No antiviral drugs or
vaccines available
 Infects B cell by binding to  Early: nonstructural proteins,
complement component C3d receptor marks the start of replication
 becomes latent in B cell and
immortalizes B cell  virus
 Late: structural components of
persistence, limited viral expression, viral capsid and glycoproteins
potential to reactivate and lytic
replicate
 Replications:
 Lytic replication, can occur both
 Antigen
 Latent: EBNA (gene
in B cell (needs reactivation) or
regulation, extrachromosomal epithelial cell (right after entry)
replication), EBER (untranslated  Marked by production of early
RNA and LMP (growth) antigen proteins
Lab Diagnosis
 Virus Isolation and Identification
 Nucleic Acid Hybridisation  identifies EBER from infected
cells
 Immortalized B cell culture
 Serology
 ELISA
 Immunoblot assay
 Immunofluorescent test
 Heterophile agglutination test
HHV-8
 Associated with Kaposi’s
Sarcoma
 KS: vascular neoplasm that
manifests in the skin and other
organs. Usually begins as a
red/purple patch that becomes
nodular and plaque-like. Most
common malignancy in AIDS
patients
 Presents at death, but not
necessarily causes it
 HHV-8 innactivates tumor
suppressor gene retinoblastoma
protein  indirectly causing KS
 Transmitted mainly through man-to-
man sexual activities and through
organ transplantation
 Lab Diagnosis:
 Biopsy
 PCR
 ELISA
 Immunoblot assay
 Indirect Immunofluorescent
 HHV-8 DNA/RNA detection
 Treatment: Ganciclovir, Cidofovir,
Foscarnet,
Gideon Cinta Fulus