Human CytomegaloVirus Characteristics

1
Human CytomegaloVirus - Characteristics

• ubiquitous among HerpesViruses
• lymphotrophic
• largest genome of all Herpes Viruses
• replicates only in human cells
• permissive cells include fibroblasts, epithelial
  cells, and macrophages
• semipermissive cells include mononuclear
  lymphocytes, the stromal cells of the bone
  marrow, and others basis of latency
• Infected cells become significantly enlarged
  cytomegaly
• Highly species-specific
• Only infected humans
• There are cytomegaloviruses specific for other
  animals

2
CytomegaloVirus - Pathogenesis

• Replicative Cycle is the same as other
  herpeviruses
• replication occurs in epithelial cells and virus
  is shed into most body fluids
• virus then infects cells like lymphocytes and
  macrophages
• virus is highly cell-associated and is
  transmitted by these cells
• Envelope glycoprotein protects virus from host
  antibody
• Binds Fc portion of immunoglobulins
• Virus establishes latent infection in monouclear
  cells and in organs such as kidney, liver, heart
  fibroblasts and mononuclear cells in these organs
• reactivation due to various factors including
  imunosuppression
• reactivation sheds virus into body fluid
  including semen, breast milk, and urine
• also reactivation often follows blood transfusion
  and organ transplants

3
Human CytomegaloVirus Clinical Diseases

• asymptomtic infection
• in most healthy individuals infection may occur
  without symptoms
• however, virus is shed these people are healthy
  carriers
• if symptoms develops they appear as mononucleosis
  or hepatitis
• Mononucleosis-like syndrome
• much like EBV with atypical lymphocytosis
• mild pharyngitis and variable lymphadenopathy
• heterophile antibody negative
• Hepatitis liver dysfunction similar to
  hepatitis, but no evidence of classical
  hepatitis viruses
• Cytomegalic Inclusion Disease
• Congenital
• Perinatal

4
CMV Cytomegalic Inclusion Disease

• Congenital
• virus crosses the placenta from mothers blood
  during primary infection (occasionally during
  reactivation)
• Generally affects the nervous and RE systems
• pathology includes microencephaly, growth
  retardation, hepatospenomegaly, and retinitis
• Intrauterine mortality approx 20
• Full term infants experience significant CNS
  defects
• unilateral or bilateral hearing loss, blindness
  and mental retardation
• the mothers of almost all infants who have these
  birth defects have had primary infection during
  their pregnancy
• this virus(CMV) is the most prevalent virus
  observed in cased of congenital disease
• approx 1/1000 infants with congenital CMV per year

5
CMV Cytomegalic Inclusion Disease

• Perinatal
• virus is acquired from cervical secretions during
  birth
• Results from virus reactivation during pregnancy
• Although they are protected by maternal antibody,
  they
• begin to secrete virus 3 - 4 weeks after birth
• Are healthy infants with no clinically disease
  carriers
• Will secrete virus chronically for many years

6
Human CytomegaloVirus Risk Factors

• Tranfusion and Transplantation Receipients
• mononucleosis or hepatitis following transfusion
  or transplantation
• often asymptomatic in healthy recipients
• virus is frequently transmitted and reactivated
  in organ transplants
• Immunocompromised Patients
• primary and secondary infection may occur in
  patients with decreased cellular immunity
• may involve the lung, eye, esophagus, or colon
• Susceptible pregnant Female
• Not immune to CMV infection

7
CytomegaloVirus - Epidemiology

• Reservoir infected humans, asymptomatic or
  symptomatic
• Media of Transmission virus has been found in
  urine, blood, throat washings, salvia, tears,
  breast milk, semen, feces, amniotic fluid,
  vaginal and cervical secretions, and various
  organs and tissues
• Major modes of transmission person-to-person
• vertical, congenital
• 10 of all newborns in the U.S.
• direct, salivary droplet
• direct, sexual
• 13 - 23 of females in venereal disease clinics
  shed virus from the cervix
• CMV is more concentrated in semen than any other
  body fluid
• 10 - 15 of adolescents are infected 50 of
  adults infected by age 35
• blood transfusion
• tissue/organ transplants

8
CytomegaloVirus - Diagnosis

• Cytology
• hallmark of CMV infection is the cytomegalic
  cell an enlarged cell in which the nucleus
  contains a dense, central, basophilic
  intranuclear inclusion body often looks like an
  owls eye
• infected cells may be found in any tissue and in
  urine
• Papaicolaou or hematoxylin-eosin stains
• Antigen Detection Rapid and Sensitive Tests
• Antigen detection using enzyme or fluorescent
  labeled monoclonal antibody
• Nucleic acid detection using similarly labeled
  DNA probes
• Serology
• Seroconversion,(antibody response) in an
  excellent marker for primary infection(IgM) or
  recurrent infection(IgG)
• Culture
• CMV grows in diploid-fibroblast cell cultures
• characteristic CPE observed in 4 - 6 weeks
• not routinely used for diagnosis much used
  epidemiologically

9
Human Herpes Virus, Type 6

• like EBV and CMV is lymphotrophic and ubiquitous
• Cellular receptor is CD46 found on T-cells,
  B-cells, glial cells, fibroblasts and
  megakaryocytes
• Also shed from oropharyngeal cells
• Not antigenically related to any other Herpes
  Viruses
• Except for HHV- 7
• HHV-6 is also a cofactor in AIDS patients causing
  mononucleosis and lymphadenopathy
• virus is present in salvia of most adults and is
  shed to children at a young age in oral secretions

10
Human Herpes Virus, type 6 Roseola

• Also known as exanthema subitumor Roseola
  infantum
• Sometimes called Sixth Disease
• an infection of T- cells where it also becomes
  latent
• symptoms (fig 51-17)
• rapid onset of fever to 103 - 105 F may last
  four days sometimes causing febrile seizures
• Fever spike is followed in 24 hours by
  generalized macular rash (exanthem)
• rash is due to delay hypersensitivity or T -cell
  action in skin
• T - cells resolve the infection, but virus
  remains latent in T -cells during the life the
  host
• Virus is shed and transmitted in oral secretions
  from asymptomatic carriers

11
Human Herpes Virus, type 6 - Epidemiology

• Human Reservoir
• Very common herpes virus
• 45 of U.S. children are infected by age 2
• 90 of adults are seropositive
• Asymptomatic shedding of virus is common
• Virus buds from lymphocytes into oral tissues
• Adults are the common source of HHV-6 to their
  children

12
ParvoViruses - Characteristics

• very small, non-enveloped, icosahedral, DNA
  viruses
• smallest of DNA viruses (18 - 26 nm)
• one linear, single-stranded DNA molecule
• the small genome(5.5 kilobases) makes these virus
  very dependent on the host cell(sometime another
  virus) for replication
• some virus particles contain the plus() strand,
  others the minus(-) strand
• only the plus() stranded viruses are infectious
• genome encodes only a few proteins, structural
  and non-structural, by an overlapping reading
  mechanism
• virus does not provide its own DNA dependent DNA
  polymerase
• must be supplied by a mitotically active cell
• viruses are replicated by mitotically active
  cells of the erythroid lineage
• bone marrow erythroid precursor cells, fetal
  liver, leukemia cells

13
ParvoViruses- Virus Cycle

• VAPs bind virus to P blood group receptors on
  erythroid precusor cells
• penetration via a type of viropexis requires
  special pits in cell membrane
• virion is uncoated in the nucleus
• mitotically active cells (S phase) polymerize a
  complementary (minus) strand of DNA thus
  providing a double stranded molecule for
  transcription of early and late proteins
• m-RNA is translated in the cytoplasm(ribosome)
  and protein products are returned to the nucleus
  for assembly or action
• cellular DNA dependent DNA polymerase replicates
  the plus and minus strands of DNA separately
• during assembly structural proteins(capsids)
  enclose both plus and minus DNA strands
  separately thus giving particles with single
  stranded DNA
• non-structural virus products cause the nuclear
  membrane and the cell membrane to degenerate
  thus releasing the viruses by lysis

14
ParvoViruses - Pathogenesis

• Parvovius, B19
• virus first replicates in the upper respiratory
  tract
• spreads via viremia to bone marrow and other
  erythroid precursor cells
• virus is cytolytic for these cells
• killing of cells and release of virus actives
  host immune response which forms the basis for
  rash and arthralgia
• Clinical Symptoms described as
• Erythrema infectiosum also known as fifths
  disease

15
Human Parvovirus, B19 Erythrema infectiousm

• Parvovirus, B19 etiological agent
• only one consistent human pathogen in this group
• Genus Erythrovirus
• Disease Progression
• Incubation period
• viremia occurs within eight days and leads to
  prodromal period
• patient is infectious
• Prodromal period
• mild influenza-like symptoms
• fever, sore throat, malaise, myalgia and slight
  drop in hemoglobin
• this is also the initial febrile period during
  which
• erythrocytes production stops for one week
• viremia releases more virus into oral and
  respiratory secretions
• thus patient is still infectious for up to 14
  days

16
Erythrema infectiosum Fifths Disease

• Disease Progression
• Symptomatic stage
• as antibody (IgM) resolves the viremia in creates
  immune complexes that precipitate out in the skin
  and joints
• thus the rash which appears on the face (slapped
  cheeks) and spreads to the extremities may last
  1 - 2 weeks in children
• in adults the rash may or may not occur, but is
  followed by polyarthritis of the hands, wrists,
  knees and ankles

17
ParvoViruses Other Clinical Diseases

• Polyarthrits
• Aplastic crisis
• occurs in patients suffering with chronic
  hemolyic anemia
• results from transient reduction in
  erythropoiesis
• which leads to reticulocytopenia last 7 - 10 days
• decrease in hemoglobin levels
• crisis accompanied by fever, malaise, myalgia
  chills, and the maculopapular rash with
  arthralgia
• Hydrops fetalis
• aplastic crisis in the fetus of pregnant females
  who are seronegative
• results in fetal anemia and congestive heart
  failure in utero

18
ParvoVirus, B19 - Diagnosis

• mostly based upon clinical presentation
• laboratory confirmation
• ELISA test for B19 IgM or IgG
• PCR coupled with gene probes are very sensitive
  in B19 genome detection

19
ParvoVirus, B19 - Epidemiology

• Erythrovirus is the only Parvovirus which infects
  humans
• Infections occur throughout the year
• Outbreaks are common in school age children
• Most infection occur between ages of 5 -19
• Mode of transmission
• Person-to-person, direct, respiratory droplet
• Person-to-person, indirect, fomites
• Virus is non-enveloped and is very stable in the
  environment in air and contaminated surfaces
• Pregnant females often acquire virus from their
  infected children

20
ParvoVirus- Control

• Stringent hygiene
• Hand-washing
• Not sharing drinking devices
• Disinfection
• There is no vaccine against human parvoviruses
• There is a vaccine against animal parvoviruses
  genus Parvovirus
• Canine parvovirus
• Feline panleukopenia virus

21
PoxViruses - Characteristics

• Largest viruses which infect humans and
  animals(300 -350 nm)
• Particle structure is most complex of all viruses
• core which contains double stranded DNA and many
  enzymes/proteins
• two membranes surround the core complex
  envelope
• Virus provides for most of its own requirements
• only DNA viruses in which the complete
  replicative cycle occurs in the cytoplasm
  complex cycle
• Thus, the virus must encode most all of the the
  enzymes needed for it replication with little,if
  any, assistance from the host cell
• the includes a viral encoded DNA dependent RNA
  polymerase
• inclusiong bodies (Guarnieri Bodies) form in the
  cytoplasm and serve as sites of DNA replication
• infected cells release about 10,000 virus
  particles upon lysis

22
PoxViruses Clinical Diseases

• Small pox
• Variola major and Variola minor Orthopoxvirus
• acquired by respiratory droplets, spreads by
  viremia to infected many tissues including the
  skin where the lesion develop to the pustule
  stage
• Cowpox
• Vaccinia Orthopoxvirus
• Molluscum contagiosum
• Molluscipoxvirus Genus
• currently the only poxvirus disease of humans
  appears as papules and nodules on the skin virus
  is transmitted by direct contact, both sexual and
  non-sexual

23
Molluscum contagiosum Clinical Disease

• Benign epidermal tumors
• Small, pink, wart-like, often umbilicated tumors
• Non-STD lesions on face, arms, back, buttock
• STD any moist genital area
• Contain semisolid caseous material
• Containing Molluscipoxvirus DNA
• Long incubation period 3-6 months
• Persistent lesions lasting up to 2 years
• Spontaneous regression
• Person-to-Person, direct, contact/sexual
• Person-to-Person, indirect, fomites (towels,
  toys)

24
Small Poxvirus - Epidemiology

• Human Reservoir
• Respiratory droplets
• Scabs from lesions
• Most common mode of transmission
• Person-to-Person, direct, respiratory droplet

25
Smallpox - Control

• Active Attenuated Vaccine chemically stabilized
• Vaccinia Virus naturally attenuated zoonotic
  strain
• Obtained from vesicular lesion of calves
• Later virus were grown in chicken embryos
• From early experiment conducted by Edward Jenner
  -1796
• First microbial disease to be eradicated via herd
  immunity from a vaccine
• Routine vaccination in the U.S ceased in 1971
• Routine vaccination in the World ceased in 1978
• Epidemiology/Control
• The importance of smallpox today is that it is
  and example of the disease which was eradicated
  by producing herd immunity through the process
  of vaccination( use of active vaccinia virus)