Human herpesviruses

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Human herpesviruses

• Three subfamilies (genome structure, tissue
  tropism, cytopathologic effect, site of latent
  infection)
• Alphaherpesvirinae
• Human herpesvirus 1 Herpes simplex type 1 HSV-1
• Human herpesvirus 2 Herpes simplex type 2 HSV-2
• Human herpesvirus 3 Varicella-zoster virus VZV
• Gammaherpesvirinae
• Human herpesvirus 4 Epstein-Barr virus EBV
  Oncogenic
• Human herpesvirus 8 Kaposis sarcoma related
  virus HHV-8 Oncogenic
• Betaherpesvirinae
• Human herpesvirus 5 Cytomegalovirus CMV
  Congenital inf
• Human herpesvirus 6Herpes lymphotropic virus
  HHV-6
• Human herpesvirus 7 Human herpesvirus 7 HHV-7

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Human herpesviruses

• Large, enveloped double stranded DNA viruses
• Icosahedral capsid
• Sensitive to acid, solvents, detergents and
  drying

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Human herpesviruses

• They have common
• Virion morphology
• Basic mode of replication
• Capacity to establish latent and recurrent
  infections, in case of EBV immortalizing
  infections
• Ubiquitous
• Usually cause benign disease especially in
  children
• In immunosuppressed people they cause significant
  morbidity and mortality

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Human herpesviruses

• -DNA polymerase -viral DNA replication -good
  target for antiviral drugs.
• -DNA replication and assemblynucleus
• -buds from nuclear membrane, released by
  exocytosis and cell lysis.
• -lytic,persistant, latent, for EBV immortalizing
  infections

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Herpes simplex virus

• Two types HSV-1 and HSV-2
• HSV can infect most types of human cells and even
  cells of other species.
• Lytic infection of fibroblasts and epitelial
  cells but latent infection of neurons
• The primary target cell mucoepitelial cells
• Site of latency neurons

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Herpes simplex virus

• Means of spread HSV-1 close contact, HSV-2 close
  contactsexual transmission!
• Generally cause infection at the site of
  infection
• HSV-1 infections above the waist
• HSV-2 infections below the waist
• Growth characteristics are different
• HSV-2 more potential for viremia

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Herpes simplex virus

• Disease initiates by direct contact, depends on
  the infected tissue (oral, brain, genital)
• Direct cytopathologic effect
• Lytic infections of most cells, latent infection
  of neurons(hides from immune response)
• Cell to cell spread-syncytia(avoids antibody)
• Cowdry type A acidophilic intranuclear inclusion
  bodies

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Herpes simplex virus

• Initiates infection through mucosal membranes or
  breaks in the skin
• Virus replicates in the cells at the base of the
  lession and infects the innervating neurons
• Travels by retrograde transport to the ganglion(
  trigeminal ganglion for oral HSV, sacral ganglia
  for genital HSV)

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Herpes simplex virus

• Then turns to initial site of infection
• May be inapparent or vesicular( vesicle fluid
  contains infectious virons)
• Tissue damage viral pathologyimmunopathology
• Heals without a scar
• Latent infection occurs in neurons

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Herpes simplex virus

• Recurrence stress, trauma, fever, sunlight)
• The virus travels back down the nerve causing
  lessions at the dermatome
• Recurrences are less severe and more localized

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• HSV-1 is common
• 90 have antibody by 2 years of age
• HSV-2 occurs later in life with sexual activity
• Physicians,nurses,dentists at risk for infection
  of fingers (herpetic whitlow)
• Immunocompromised people and neonates at risk of
  disseminated, life-threateneing disease.

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Laboratory diagnosis

• Cytology and histology Tzanck smear(scraping of
  the base of a lesion), Papanicolaou smear or
  biopsy specimen
• Cytopathic effects syncytia, ballooning of
  cytoplasm, Cowdry A intranuclear inclusions
• Direct antigen detection immunofluorescence
  method or immunoperoxidase method
• DNA in situ hybridization or PCR in tissue or
  vesicle fluid

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Laboratory diagnosis

• Virus isolation not routine now
• Serologyprimary infection, type specific
  antibody by ELISA (differentiates HSV-1 and HSV-2)

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Varicella-Zoster

• Chickenpox(varicella)
• With recurrence herpes zoster-shingleszona
• Primary target cell mucoepitelial cell
• Site of latency neuron
• Means of spread respiratory and close contact
• Viremia occurs after local replication skin
  lessions over the entire body

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Varicella-Zoster

• Primary VZV infection mucosa of respiratory
  tract
• Viremia
• Reticuloendotelial system,liver,spleen
• 11-13 days later secondary viremia
• Virus is spread through the body and
  skinrashfeversystemic symptoms

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Varicella-Zoster

• Latent in dorsal root or cranial nerve ganglia
  after primary infection
• Reactivates in older adults and in patients with
  impaired immunity.
• On reactivation a vezicular rash along the
  entire dermatome
• Children and leukemia VZV more serious and more
  disseminated disease

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Varicella-Zoster

• Extremely communicable
• Rates of infection exceeds 90 among household
  contact
• Contagious before and during symptoms.
• HZ develops in 10-20 of people infected with VZV
  and contains viable virus.

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Varicella-Zoster

• Laboratory diagnosis
• Cytology
• Virus isolation difficult
• NAT
• Serology
• Treatment
• ACV,famciclovir and valacyclovir
• Prophylaxis VZIGvaricella-zoster
  immunoglobulinimmunosuppressed patients
• A live attenuated vaccine(Oka strain)

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Epstein-Barr Virus

• Heterophile antibody-positive infectious
  mononucleosis
• Chronic disease
• Associated with endemic Burkitts lymphoma,
  Hodgkins disease, nasopharyngeal carcinoma,
  B-cell lymphomas in patients with acquired or
  congenital immunodeficiencies.
• Hairy oral leukoplakia
• Mitogen for B cells and immortalizes them

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Epstein-Barr Virus

• Gammaherpesvirinae
• Primary target cell B cells and epitelial cells
• Site of latency B cell
• Means of spread saliva (kissing disease)
• Limited host range and tissue tropism receptor
  for C3d component of the complement system (CR2
  or CD21) which is expressed on B cells of humans
  and some epitelial cells of oro- and nasopharynx.

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EBV-associated neoplasms

• Geographic distribution
• Co-factor?
• Endemic Burketts lymphoma Africamalaria
• Nasopharyngeal carcinoma China

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Laboratory diagnosis

• Heterophile antibody results from nonspecific
  activation of B cells by EBV
• IgM antibody recognizes Paul-Bunnell antigen on
  sheep, horse and bovine erythrocytes not on
  guinea pig kidney cells
• Detected at the end of first week , lasts for
  several months
• Monotest, ELISA specific antibodies
• VCA-IgM, antibody to early antigen (EA) recent
  infection
• VCA-IgG, EBNA previous infection
• PCR

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Cytomegalovirus(CMV)

• Betaherpesvirnae lymphotropic
• Primary target cell monocyte, lymphocte,
  epitelial cell
• Site of latency monocyte, lymphocyte and?
• Means of spread close contact, transfusions,
  tissue transplant and congenital

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Clinical findings

• Predominant presentation asymptomatic
• Neonates deafness, mental retardation
• Immunosuppressed patients disseminated dissease,
  severe disease (pneumonia, retinitis, colitis,
  esophagitis)

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Congenital infection

• An important cause of congenital disease
• Serious birth defects is high if primary
  infection occurs during pregnancy
• Microcephaly, intracerebral calcification,hepatosp
  lenomegaly,rash(cytomegalic inclusion disease),
  unilateral or bilateral hearing loss, mental
  retardation
• CMV in the urine in the first week (culture,PCR)

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Laboratory tests

• Cytology and histology OWLs eye inclusion
  body basophilic intranuclearUrine not so
  sensitive
• Antigen in peripheral leucocytes
• DNA by PCR
• Cell culture Human diploid fibroblasts
• Serology primary infection(IgM by ELISA)

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Human herpesvirus 6

• Betaherpesvirinae
• Lymphotropic , ubiquitous
• Primary target cell T cells and ?
• Site of latency T cells and ?
• Means of spread Respiratory, close contact
• Exanthema subitum roseola
• A mononucleosis syndrome and lympadenopathy

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Human herpesvirus 8

• HHV-8 DNA sequences were discovered by PCR in
  biopsy specimens of
• Kaposis sarcoma (characteristic opportunistic
  diseases associated with AIDS)
• Primary effusion lymphoma (rare type of B-cell
  lymphoma)
• Multicentric Castlemans disease

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Human herpesvirus 8

• Kaposis sarcoma-related virus
• Primary target cell Lymphocyte and other cells
• Site of latency?
• Means of spread close contact, sexual, saliva?
• Limited to certain geographic areas (Italy,
  Greece, Africa) and AIDS

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Human herpesvirus 8

• Laboratory diagnosis
• Serology specific antibodiesIFA IgG,IgM
• HHV-8 DNA by PCR

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Antivirals

• Herpes Simplex 1 and 2 Acyclovir
• Penciclovir
• Valacyclovir
• Famciclovir
• Adenosine arabinoside (ara-A)
• Trifluridine

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Antivirals

• Varicella-Zoster Virus Acyclovir
• Famciclovir
• Valacyclovir
• Varicella-zoster immune globulin (VZIG)
• Zoster immune plasma
• Live vaccine
• Epstein-Barr Virus None

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Antivirals

• Cytomegalovirus
• Ganciclovir
• Valganciclovir
• Iododeoxyuridine
• Foscarnet
• Trifluridine
• Cidofovir

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Herpesvirus simiae(B virus)

• Asian monkeys
• Bites, saliva
• Encephalopathy in humans
• fatal