Chapter 25: Enveloped DNA Viruses

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Chapter 25 Enveloped DNA Viruses

• 3 major Enveloped DNA Virus Families
• Herpesviridae
• Poxiviridae
• Hepadnaviridae (Chapter 26)

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Herpesviridae

• Largest family of DNA viruses that affects humans
• Infections are very common viruses are
  ubiquitous
• Once you get Herpes virus, you always have it
  always have the Herpes infection
• 8 human herpesvirus species known, each w/
  ability to enter a latent state following
  1infection of their natural host be
  reactivated _at_ a later time.

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Herpesviridae

• General Characteristics of HerpesViruses
• Icosahedral capsid enclosed in lipoprotein
  envelope
• Tegument amorphous proteinaceous material lying
  between envelope and capsid
• Contains virus-coded enzymes and transcription
  factors
• Genome single molecule of linear, ds-DNA

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Herpesviridae

• Classification of HerpesViruses
• a-Herpesvirinae (Herpes Simplex Virus group)
• Rapid, cytolytic growth cycle establish latency
  in Nerve Ganglia
• Lytic infections in permissive cells
  Fibroblasts Epithelial cells
• Members HSV-1, HSV-2 and VZV
• ß-Herpesvirinae (Cytomegalovirus group)
• Slow replication cycle, resulting information of
  multinucleated, giant host cells
• Latency established in non-neuronal tissues, 1
  lymphoreticular cells glandular tissues
• Members HCMV, HHV-6 and HHV-7
• ?-Herpesvirinae (Lymphoproliferative group)
• Replicate in mucosal epithelium, where latency is
  also established
• Induction of cell proliferation in lymphoblastoid
  cells
• Members EBV and HHV-8 (recovered from Kaposi
  Sarcoma)

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Herpesviridae

• Nature of a-HerpesViruses
• Large, enveloped ds-DNA viruses
• Envelope obtained from host cell nuclear
  membrane released by exocytosis or lysis
• Genome encodes for proteins that regulate viral
  mRNA synthesis by host cells DNA-dependent RNA
  polymerase
• HSV genome also encodes for proteins that
  regulate DNA replication provides for own
  DNA-dependent DNA polymerase
• Initially uses host cells DNA-dependent RNA
  polymerase to form viral mRNA, which is
  translated into early proteins, such as viral
  DNA-dependent DNA polymerase
• Genome encodes for proteins that slow down or
  stop host cells ability to synthesize own DNA,
  RNA and proteins
• Virus DNA replication assembly BOTH occur in
  nucleus
• Virus buds thru nuclear membrane and is released
  from cell by exocytosis or lysis
• When virus released, does NOT get envelop from
  plasma membrane of host cell it was already
  acquired from nuclear membrane

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Herpesviridae

• Summary of HSV Viral Cycle
• Viral envelope glycoporoteins bind (adsorb) virus
  to host cell receptors
• Fusion of viral envelope w/ host cell membrane
  removal of envelope and release of nucleocapsid
  tegument proteins into the cytoplasm
• One tegument protein induces a host cell RNase
  that degrades host cell mRNA, shutting off host
  cell protein synthesis
• Upon fusion, virion also releases proteins that
  promote initiation of viral gene transcription,
  thus beginning replicative cycle
• Nucleocapsid is transported to a nuclear pore,
  thru which viral DNA is released into the
  nucleus. Another tegument protein is an
  activator of cellular RNA polymerase that causes
  the enzyme to initiate transcription of immediate
  early viral genes, coding for a variety of
  regulatory functions. Then delayed early viral
  genes expression enzymes for replication of
  viral DNA

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Herpesviridae

• Summary of HSV Viral Cycle
• Early proteins facilitate transcription of
  viral genome and include the DNA-dependent DNA
  polymerase
• Late proteins structural and synthesized after
  DNA replication
• Acquisition of viral envelope
• Newly synthesized envelope proteins accumulate on
  nuclear membrane
• Nucleocapsids, now assembled, acquire their
  envelopes by budding thru nuclear membrane
• Enveloped nucleocapsids exit the host cell via
  exocytosis or cell lysis (host cell dies)
• Latency all herpesviruses can undergo this
  alternative infection cycle, entering a quiescent
  state from which they can be reactivated
• Cells that promote latency semipermissive
  cells restrict viral transcription of early
  late proteins
• Occurs in NERVE CELLS

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Herpes Simplex Virus, Types 1 2

• HSV infect most types of human cells
• Lytic infection in permissive Fibroblasts and
  Epithelial cells
• Latent infection in semipermissive neurons
• HSV-1 HSV-2 gt common human pathogens that
  cause painful, but benign manifestations
  recurrent disease
• CLASSIC manifestation of lesions is that of clear
  vesicle on an erythematous base, which progresses
  to pustular lesions, ulcers and crusted lesions

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Herpes Simplex Virus, Types 1 2

• Epidemiology
• Reservoir humans w/ acute asymptomatic
  infection person is infected for a life-time d/t
  latency
• HSV is an exclusive human disease
• Mode of Transmission p-p via direct contact w/
  virus-containing secretions, both sexual
  non-sexual fingers exchange of oral fomites
  autoinnocualtion from oral/genital lesions to
  other body areas (e.g., eyes) contact w/ lesions
  on mucosal or cutaneous surfaces
• Enveloped virus gt is readily inactivated by
  drying, detergents and other adverse conditions
• Transmission of HSV-1 via kissing or
  saliva-contaminated fingers eating utensils,
  toothbrushes, drinking glasses
• Typical transmission adult w/ active recurring
  lesion touches/kisses a child gt large s or
  virus are present in vesicular fluids exudate
  from ulcerative lesions
• Transmission of HSV-2 is primarily by sexual
  contact
• HSV-2 found in 10-15 cases of STDs in clinics
• Also infected ?s can transmit virus to infants
  during delivery

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Herpes Simplex Virus, Types 1 2

• Pathogenesis
• HSV-1 HSV-2 multiply in epithelial cells of
  mucosal surface onto which they were innoculated
  ? production of vesicles or shallow ulcers
  containing virus
• Immune response via cytotoxic T-cells
  (lymphocytes) in immunocompetent indiv.
• Latency usually estd. in regional ganglia as
  result of entry of infectious virions into
  sensory neurons that terminate _at_ site of infection

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Herpes Simplex Virus, Types 1 2

• Clinical Significance
• HSV-1 generally causes lesion above waist
• HSV-2 generally causes lesions below waist
• Primary Infections of Upper Body
• Lesions consists of vesicles shallow ulcers
• Accompanied by fever, myalgia and malaise
• Gingivostomatitis (Herpes Labialis) m/c
  symptomatic infection of upper body in children
• Pharyngitis or tonsilitis m/c symptomatic
  infection in adults
• Keratoconjunctivitis
• HSV-1 infection of eye 2nd m/c cause of corneal
  blindness (after trauma), corneal scarring
• Herpetic Gladiatorium
• Herpes infection of the body d/t skin abrasions
• Seen in wrestlers burn victims
• Herpetic Whitlow
• Herpes infection of fingers /or hands
• Historically, dentist are _at_ high risk long
  history of exposure before wearing gloves
• Chiropractors esp. working w/ pts w/ shingles

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Herpes Labialis

• m/c clinical disease caused by HSV-1
• AKA cold sore or fever blister
• Lesion
• Clear vesicles on erythematous base, which
  ulcerates and crusts over
• Location around mouth or oral cavity
• Often re-occurs when virus buds from sensory
  neuron, specifically CN V2 (Maxillary Branch of
  the Trigeminal Nerve)
• 1 infection
• Sxs fever, pain and irritability usu. persist
  for 1 week, followed by gradual healing during
  2nd week
• Virus passes along Nerve fibers to regional
  ganglia w/ Gingivostomatitis Trigeminal
  Ganglia involved and virus becomes sequestered in
  latent form there
• Virus cant be detected in latent form no sxs
• Recurrence of latent infection activation by
  emotional stress, trauma, UV-B sunlight, fear,
  cold winds, hormonal ?s
• Virus moves ? nerve fiber to cause recurring skin
  lesions _at_ original inf. site

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Herpes Simplex Virus, Types 1 2

• Primary Infections of Upper Body
• Herpetic encephalitis
• VIREMIA allows spread of virus to CNS, brain in
  particular
• Destruction of temporal lobe, causing seizures,
  focal neurological abnormalities, HA, fever
• Untreated 70 mortality rate
• Primary infections of Lower Body
• Herpes genitalis Genital Herpes
• Infection w/ HSV-2 involving urogenital skin
  mucous membranes
• Majority of infections asymptomatic
• Symptomatic infections painful, itching,
  vesiculoulcerative lesions upon genital tissue
• Males glans or shaft of penis sometimes in
  urethra
• Females vulva, cervix (mucoid discharge
  possible), perianal area, inner thighs and vagina
• Accompanying by fever, malaise, myalgia,
  inguinal adenitis (lymph node swelling)
  possible b/c of transient viremia
• Infections heal spontaneously in 2-4 weeks
• Recurrent infections common, but milder than 1
  infection
• Periodic recurrence d/t budding of HSV-2 from
  Sacral N. ganglia

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Herpes Simplex Virus, Types 1 2

• Latency virus infects innervating sensory
  neurons by retrograde transport to ganglia
• HSV-1 in Trigeminal Ganglia (CN V2) for oral HSV
• HSV-2 in Sacral or Lumbar Ganglia for Genital
  Herpes
• Reactivation
• Hormonal ?s, fever, STRESS, and physical damage
  to neurons gt all known triggers for viral
  reactivation and replication of latent virus
• Stress causes reactivation of viral genome newly
  synthesized virions are transported ? the axon to
  nerve endings from which the virus is released,
  infecting the adjoining epithelial cells
• Characteristic lesions produced in same area as
  1 lesions, but less severe
• HSV-1 lesions occur as clusters of vesicles _at_
  border of lips Herpes labialis or cold sores,
  fever blisters frequency 0 ? several/year
• HSV-2 genital infections occur w/ greater
  frequency (monthly), often asymptomatic, but
  still w/ viral shedding
• Circulating Ab does NOT prevent recurrence

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Herpes Simplex Virus, Types 1 2

• Laboratory Identification/Dx
• Clinical observation of the vesicular lesions
• Isolation of HSV from tissue scrapping sample
• Characteristic inclusion body in nucleus of
  infected cell can be stained Intranuclear
  inclusion body Cowdry Type A intranuclear
  Inclusion Body
• Treatment/Prevention
• Several antivirals drugs available that are DNA
  inhibitors none cure the latent infection, but
  can minimize asymptomatic viral shedding and
  recurrence of symptoms
• Prevention by avoidance of contact w/ potential
  virus-shedding lesions safe sexual practice
• No vaccine available

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Varicella-Zoster Virus

• Causative agent for varicella or chicken pox
• Reactivation of the latent infection produces
  shingles
• Classified in the a-Herpesvirinae subfamily of
  HSV
• Similar to HSV, but has smaller genome,
  replicated slowly, infects narrower range of
  cells
• Establishes latent infections in neurons
• Recurrent infection along innervated dermatomes
• Vesicular, blister-like lesions
• Requires cell-mediated immunity to control and
  prevent
• Epidemiology
• 1 Mode of Transmission p-p, direct via
  respiratory droplets
• 2 Mode of Transmission p-p, direct contact w/
  active vesicle
• Systemically spread thru entire body by viremia
• VZV differs from HSV in that it produces a viremia

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Varicella-Zoster Virus

• Pathogenesis
• 1 infection in cells of respiratory mucosa
  epithelial cells fibroblasts
• Cell-to-cell spreading to region lymph nodes
• From lymph nodes to the blood 1 Viremia ? then
  virus to reticuloendothelial system, where it
  grows in liver, spleen, BM
• 2 Viremia moves the virus from RES via the blood
  to entire body, including the skin
• Symptoms include fever, malaise, and
  vesiculopustular rash that appears in successive
  crops beginning on head/neck, than thorax, and
  finally extremities

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Varicella-Zoster Virus

• Pathogenesis
• Virus becomes Latent in semi-permissive cells of
  dorsal root ganglion (drg) /or cranial nerve
  ganglia (CN V in particular)
• Antibody limits viremia spread, but cell-mediated
  immunity is required for complete resolution
• Infection in adult is more serious than in
  children
• Reactivation VZV replicated and is released
  along the neural pathways to the skin, causing a
  vesicular rash along the entire dermatome
  Shingles

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Varicella-Zoster Virus

• Clinical significance
• Chickenpox (Varicella Primary Infection)
• Childhood exanthem
• Mild childhood disease w/ sxs of fever
  maculopapular rash (follows 14-day incubation)
• Hallmark of Varicella Vesicle
• dew-drop on rose pedal lesion small red spots
  in them
• Becomes pustular crusts over, forming scab
• Successive crops of vesicles appaer over 3-5
  days at any given stage, all lesions can be
  observed
• Lesions begin on scalp, spread over the face
  neck to trunk, where they are most severe and
  noticeable

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Varicella-Zoster Virus

• Clinical significance
• Shingles (Herpes zoster Recurrent infection)
• Recurrent manifestation of VZV acquired earlier
  in life as chickenpox
• Virus buds thru nerves along the dermatomes or
  along CN V
• Painful vesicular lesions having a erythematous
  base develop along these nerve
• Postherpetic neuralgia
• Chronic pain along the dermatomes, which persists
  from years following a bout of shingles
• Occurs in 30 pts gt65 yao

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Varicella-Zoster Virus

• Laboratory Identification/Dx
• Cytology
• Presence of Cowdry Type A intranuclear Inclusion
  Bodies
• Tznack smears from base of vesicles reveal
  multinucleated giant cells (syncytia formation)
• Ag detection
• Serology presence of IgM or 4-fold ? in IgG
• Treatment/Prevention
• Inmunocompromised antiviral drug
• VZ Ig vaccination in susceptible individuals
  (immunocompromised) no effect on zoster

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Human Cytomegalovirus

• Member of the ß-Herpesvirinae subfamily of
  Herpesvirinae family
• Is the LARGEST known virus to infect humans
  largest genomes of all herpesviruses
• Longer replication cycle and infected cells are
  greatly enlarged and mulitnucleated
• Cytomegalo cell of great size name for classic
  cytomegalic inclusion disease derives from
  propensity for massive enlargement of
  CMV-infected cells

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Human Cytomegalovirus

• Nature of the organism
• Linear, ds-DNA housed in icosahedral capsid
• Lipid envelope contains gps that facilitate
  attachment and entry into host cell
• Pathogenesis
• CMV is lymphotrophic affinity for lymphocytes
• Replicates only in human cells
• Permissive cells fibroblasts, epithelial cells,
  macrophages
• Semi-permissive cells mononuclaer lymphocytes,
  stromal cells of BM, leukocytes cells of kidney,
  heart, lung
• CMV readily establishes persistent and latent
  infections

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Human Cytomegalovirus

• Pathogenesis
• Replicative cycle same as for other
  Herpesviruses
• Occurs in epithelial cells and virus is shed in
  most body fluids (Viremia when into blood)
• Virus then infects lymphocytes and macrophages
• Latent infection is established in mononuclear
  lymphocytes and fibroblasts in organs, such as
  Kidney, Heart, and Lung
• Reactivation d/t various factors like
  immunosuppresion
• Reactivation often follows blood transfusion and
  organ transplants

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Human Cytomegalovirus

• Epidemiology
• Infection in children is usually asymptomatic
• Virus is shed in tears, urine, saliva, semen,
  breast milk, vaginal secretions virtually any
  body fluid
• Transmission is by intimate contact w/ these
  bodily fuilds saliva m/c
• Transmission also by sexual intercourse, blood
  transfusion, organ transplants CMV can also
  cross placenta and infect neonate in utero of
  newborn via breast milk
• Mode of Transmission p-p direct (slivary
  droplet), vertical (congenital), direct (sexual),
  blood transfusion, tiss/organ transplant

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Human Cytomegalovirus

• Clinical Significance
• Cytomegalo Inclusion Disease
• Asymptomatic Infection
• In most healthy people no symptoms
• If sxs develop mono or hepatits
• Mononucleosis Syndrome
• Similar to EBV w/ atypical lymphocytosis
• Mild pharyngitis and variable lymphadenopathy
• Sxs malaise, myalgia, fever, liver dysfunction,
  lymphocytosis, subclinical hepatitis
• Heterophile-Negative Mononucleosis
• Distinguishes Heterophile-Positive Mononucleosis
• Hepatitis
• Liver dysfunction similar to hepatitis, but NO
  evidence of hepatitis virus

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Human Cytomegalovirus

• Clinical Significance
• Congenital
• HCMV is the m/c intrauterine viral infection
• Vertical transmission mother ? infant
• Virus crosses placenta from mothers blood
  primary infection
• Virus ascends from cervix during reoccurrence
• CMV is the most prevalent viral cause of
  congenital disease
• Pathology
• Microencephaly
• Intracerbral calcifications
• Hepatosplenmegaly
• Rash

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Human Cytomegalovirus

• Clinical Significance
• Transfusion Transplantation Recipients
• Mononucleosis or hepatitis following blood
  transfusion
• Virus is frequently transmitted reactivated in
  organ transplants
• Immunocompromised patients
• 1 and 2 infections may occur in pts w/
  decreased cellular immunity
• Cancer pts
• AIDS pts

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Human Cytomegalovirus

• Laboratory Identification/Dx
• Cytology
• Cytomegalic cell hallmark
• Enlarged cell in which nucleus contains a dense,
  central, basophilic intranuclear inclusion body
  resembled Owls Eye
• Ag detection
• PCR analysis
• Enzyme of fluorescent labeled monoclonal Ab
• Serology
• Looking for IgM or IgG Abs
• Culture
• CMV grows in diploid-fibroblast cell cultures
• Characteristic CPEs seen in 4-6 weeks
• Not routinely done

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Human Herpesvirus Type 6 7

• Members of ß-Herpesvirinae
• Both are causative agents of Roseola Infantum
  (exathem subitum)
• Lymphotrophic and ubiquitous
• 45 of U.S. children are seropositive by age 2
• An infection of T-cells
• Symptoms
• Rapid onset of fever to 103-105F may last 4-5
  days
• Fever is followed by generalized rash (exathem)
  in 24 hours lasts 24-48 hours
• Rash is d/t delayed hypersensitivity of T-cell
  activation in the skin
• T-cells resolve the infection, but virus may
  remain latent in T-cells for a life time.
• HHV-6 is also a co-factor in AIDS pts causing
  Mono or lymphadenopathy
• Early HIV co-infection w/ HHV-6 Terminal HIV
  (encephalitis)
• Virus is shed via oral secretion for adults to
  children

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Human Herpesviruse Type 8

• Does not occur as frequently as the other herpes
  viruses in the normal, healthy population
• Virus genome /or viral proteins have been
  detected in gt90 of pts w/ Kaposi Sarcoma

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Epstein-Barr Virus

• Member of ?-Herpesvirinae subfamily of
  Herpesvirinae family of DNA viruses
• Ubiquitous virus
• Etiological agent for Infectious Mononucleosis
  (kissing disease) in young adults
• Nature of the organism
• Enveloped virus w/ linear, ds-DNA
• Easily disrupted by acids, detergents and
  desiccation transmission is effectively
  accomplished via intimates contact and saliva
• DNA core surrounded by icosahedral nucleocapsi
• Very limited host range affinity for C3d
  component of C system C3d is expressed on
  B-cells and epithelial cells of oropharynx and
  nasopharynx

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Epstein-Barr Virus

• Epidemiology
• Reservoir humans, EBV only infects humans
• Humans can be both symptomatic asymptomatic
• Mode of Transmission p-p, direct, saliva
  intimate oral contact
• Is kissing disease b/c increased incidence in
  adolescents and young adults who exchange saliva
• 70 of U.S. population is infected by age 30
• 100,000 college undergraduate students infected
  each year
• Children w/ subclinical disease infected _at_
  early age by sharing drinking glasses from
  parents
• High risk for lymphoproliferative disease
  disorders initiated by EBV in
• Transplant pts who are immunocompromised
• Genetically immunodeficient patients
• AIDS patients

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Epstein-Barr Virus

• Pathogenesis
• Productive infection of B-cells of oropharynx gt
  promotes shedding of virus into the saliva then
  transmission of virus to other hosts
• Viremia is established to spread the virus to
  other B-cells in lymphatic tissue and blood
• EBV is a B-cell mitogen stimulated growth
  prevents apoptosis stimulated rapid growth of
  B-cells
• Interaction between the B-cell and EBV does NOT
  destroy the B-cell, but rather transforms the
  B-cell. The transformed B-cells contain many
  copies of EBV DNA, proliferate rapidly and have
  EBV Ags on cell membrane

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Epstein-Barr Virus

• Pathogensis
• LYTIC infections occur in permissive cells,
  mostly epithelial cells
• LATENT infections occur in semipermissive
  B-cells or non-permissive B-cells
• 2 infection subtypes in this subfamily
• EBV-1
• EBV-2

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Epstein-Barr Virus

• Clinical Disease
• Infectious Mononucleosis
• m/c manifestation of EBV Kissing Disease
• Incubation period 3-7 weeks
• Onset is gradual, up to 1 week in duration
  (malaise, HA, fatigue, Low grade fever)
• Acute phase 1-3 weeks in duration
• Intermittent high fever, generalized weakness,
  severe sore throat, swollen lymph nodes, atypical
  lymphocytes

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Epstein-Barr Virus

• Clinical Disease
• Infectious mononucleosis
• Summary of Signs Symptoms m/c complaint
  FATIGUE
• High fever
• Generalized malaise
• Exudative pharyngitis and tonsilitis
• Lymphademopathy - lymph node swelling
• Often heptosplenomegaly enlargement of liver
  and spleen
• Occasional rash
• Lymphocytosis gt ??? of T-lymphocytes in blood
• 10-80 of these are atypical Atypical
  Lymphocytes or Downey Cells enlarged T
  lymphocytes w/ eccentric nuclei and vacuolated
  cytoplasm
• Heterophile () Heterophile Ab specific for EBV
• Nonspecific Abs, including IgM Ab, that
  recognizes Paul-Bunnel Ag on sheep, horse and
  bovine Erythrocytes (RBCs)

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Epstein-Barr Virus

• Clinical Disease
• Infectious Mononucleosis
• Rarely fatal in healthy people, but can cause
  serious complications
• Neurological disorders
• Laryngeal obstruction
• Splenic rupture
• Meningoencephalitis
• Guillian-Barre Syndrome (ascending paralysis)

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Epstein-Barr Virus

• Other Clinical Diseases
• Chronic mono-like disease
• Characterized by chronic fatigue low grade
  fever, HAs and sore throat may also be present
• Lymphoproliferative diseases
• Hairy Oral Leukoplakia
• Productive infection of epithelial cells in
  mouth, esp. tongue
• An opportunisitic manifestation that occurs in
  AIDS pts
• (African) Burkitts Lymphoma
• m/c outcome of EBV exposed to non-permissive
  B-cells get tumor formation (lymphoma) B-cell
  proliferation in lymphatics of the jaw face
  mostly seen in children
• Adults may occur in abdomen get abdominal
  tumors
• Malaria seems to enhance this in Africa endemic
  in children living in Malaria regions of
  Sub-Saharan Africa

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Epstein-Barr Virus

• Other Clinical Diseases
• Lymphoproliferative Diseases
• Hodgkins Lymphoma
• Expression of EBV outside Africa
• Sxs similar to B.L.
• Nasopharyngeal carinoma
• Seen in Chinese males
• Tumor of epithelial origin
• Lymphocytic pneumonia

41
Epstein-Barr Virus

• Laboratory Clinical Dx
• Based on symptoms
• The finding of atypical lymphocytes (Downey
  Cells)
• Persistence of lymphocytosis, Herterophile Ab,
  and Ab to EBV Ags
• Sxs extreme fatigue, pharyngitis, lymphadenosis
  (swollen lymph nodes), high fever,
  hepatosplenomegaly gt adolescent, young adults
• Lymphocytosis 60-70 mononuclear cells w/ 30
  Atypical lymphocytes Earliest indicator of
  disease
• Ag detection DNA probes, immunofluorescence
• Serology
• Heterophile Ab is present by end of 1st week and
  is EXCELLENT indicator of EBV infection in adults

42
Epstein-Barr Virus

• Treatment Prevention
• No effective tx for EBV no viral vaccine
• Bed rest is BEST during acute phase
• In children less severe infection ? immunity
  developed lifelong early exposure may be a
  means of preventing more severe infections and
  symptomatic disease.
• Contact physical activities should be avoided b/c
  a swollen spleen could rupture

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Poxviridae

• Variola virus etiological agent for Small Pox,
  which has been eradicated!
• Small pox 1st disease to be controlled by
  immunization its eradication is one of the
  greatest triumphs of Medical Epidemiology
• Variola virus only DNA virus that replicates in
  the CYTOPLASM
• Virion carries its own DNA-dependent RNA
  polymerase to allow for viral replication to
  occur in the cytoplasm
• Inclusion bodies (Guariniers) serve as sites of
  DNA replication in the cytoplasm (Cytoplasmic
  Factories)
• Clinical
• Small Pox eradicated
• Molluscum Contagiosum
• Only poxvirus disease seen today
• Etiological agent Molluscum contagiosum virus
• Benign epidermal tumor that occurs only in humans
• Appears as papules nodules on skin have
  central casseous plug that can be squeezed out
  (expressed)
• M/c on trunk, genitalia, proximal extremities
• Lesions itch - autoinnoculation