Viral Infections: an overview

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Viral Infections an overview

• Dr. Gerrard Uy

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Defining a Virus

• Viruses consist of a nucleic acid surrounded by
  one or more proteins
• obligate intracellular parasites they can
  replicate only within cells
• Many human viruses are simply composed of a core
  and a capsid
• Genes contain either DNA or RNA

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RNA Viruses DNA Viruses
Picornaviruses Poliovirus Coxsackievirus Echovirus Enterovirus Rhinovirus Hepatitis A virus Herpesviridae Herpes simplex virus types 1 and 2b Varicella-zoster virusc Epstein-Barr virusd Cytomegaloviruse Human herpesvirus 6 Human herpesvirus 7
Calciviridae Norwalk agent Hepatitis E virus Hepadnaviridae Hepatitis B virus
Togaviridae Rubella virus Eastern equine encephalitis virus Western equine encephalitis virus Papovaviridae Human papillomaviruses JC virus BK virus
Flaviviridae Yellow fever virus Dengue virus St. Louis encephalitis virus West Nile virus Hepatitis C virus Hepatitis G virus Poxviridae Variola (smallpox) virus Orf virus Molluscum contagiosum virus
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RNA Viruses DNA Viruses
Coronaviridae Coronaviruses Adenoviridae Human adenoviruses
Rhabdoviridae Rabies virus Vesicular stomatitis virus Parvoviridae Parvovirus B19
Filoviridae Marburg virus Ebola virus
Paramyxoviridae Parainfluenza virus Respiratory syncytial virus Newcastle disease virus Mumps virus Rubeola (measles) virus
Orthomyxoviridae Influenza A, B, and C viruses
Bunyaviridae Hantavirus California encephalitis virus Sandfly fever virus
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Viral Infection

• Transmission
• capsid and envelope of a virus protect its genome
  
• Most common viral infections are spread by
• direct contact
• by ingestion of contaminated water or food
• by inhalation of aerosolized particles
• Animals are important reservoirs and vectors for
  transmission of viruses causing human disease

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Viral Infection

• Primary Infection
• usually lasts from several days to several weeks
• enterovirus, mumps virus, measles virus, rubella
  virus, rotavirus, influenza virus, AAV,
  adenovirus, HSV, and VZV are cleared from almost
  all sites within 34 weeks
• AAV, EBV, or cytomegalovirus (CMV) can last for
  several months
• HBV, HCV, hepatitis D virus (HDV), HIV, HPV, and
  molluscum contagiosum virus extend beyond several
  weeks

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Viral Infection

• Primary Infection
• Disease manifestations usually arise as a
  consequence of viral replication and the
  resultant inflammatory response
• are cleared by nonspecific innate and specific
  adaptive immune responses
• host is usually immune to the disease
  manifestations of reinfection by the same virus

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Persistent and Latent Infections

• HCV RNA polymerase and HIV reverse transcriptase
  have high mutation rates
• generation of variant genomes that evade the host
  immune response facilitates persistent infection
• DNA viruses lower mutation rates
• ability to establish latent infection and to
  reactivate from latency

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Persistent and Latent Infections

• latency is defined as a state of infection in
  which the virus is not replicating
• HPVs establish latent infection in basal
  epithelial cells

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Persistent and Latent Infections

• Herpesviruses latent infection is established
• in nonreplicating neural cells (HSV and VZV)
• in replicating cells of hematopoietic lineages
  EBV and probably CMV, HHV-6, HHV-7, and Kaposi's
  sarcomaassociated herpesvirus (KSHV, also known
  as HHV-8).

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Persistent Viral infections and Cancer

• estimated to be the root cause of as many as 20
  of human malignancies
• Most hepatocellular carcinoma is now believed to
  be caused by chronic inflammatory, immune, and
  regenerative responses to HBV or HCV infection
• Almost all cervical carcinoma is caused by
  persistent infection with "high-risk" genital HPV
  strains
• EBV infection also plays a role in the long-term
  development of certain B lymphocyte and
  epithelial cell malignancies

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Resistance to Viral Infections

• Initial response is not virus-specific
• Physical
• cornified layers of the skin and by mucous
  secretions that continuously sweep over mucosal
  surfaces
• Cellular
• IFNs are induced and confer resistance
• cytokines may be chemotactic to inflammatory and
  immune cells

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Resistance to Viral Infections

• By 710 days after infection, virus-specific
  antibody responses develop
• virus-specific HLA class IIrestricted CD4
  helper T lymphocyte responses, and virus-specific
  HLA class Irestricted CD8 cytotoxic T
  lymphocyte responses
• Antibody and complement can also lyse
  virus-infected cells that express viral proteins
  on their surface

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• host inflammatory and immune response contributes
  to the symptoms, signs, and other
  pathophysiologic manifestations of viral infection

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Diagnostic Virology

• Serology
• Viral Isolation
• Acute- and convalescent-phase sera with rising
  titers of antibody to virus-specific antigens
• shift from IgM to IgG antibodies

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Diagnostic Virology

• ELISA (Enyme-Linked Immunosorbent Assay)
• generally use specific viral proteins that are
  most frequently targeted by the antibody response
• amount of antibody can then be quantitated by the
  intensity of a color reaction mediated by the
  linked enzyme

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• Virus isolation
• depends on the collection of specimens from the
  appropriate site
• the rapid transport of these specimens in the
  appropriate medium to the virology laboratory
• Rapid transport maintains viral viability and
  limits bacterial and fungal overgrowth.

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Treatment

• Multiple steps in the viral life cycle can be
  effectively targeted by antiviral drugs
• synthesis of the HIV provirus
• block maturation of the HIV polyprotein
• preventing a conformational change required for
  virus fusion
• preventing release of viral RNA early during
  infection
• Prevent efficient release of mature virions

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Immunization

• Smallpox
• Poliovirus
• Measles
• Influenza
• Chickenpox
• HBV
• Mumps, rubella

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Guillain-Barre Syndrome
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Guillain-Barre Syndrome

• Acute, frequently severe, and fulminant
  polyradiculopathy
• Autoimmune in anture
• Males have higher risk than females

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Clinical Manifestation

• Rapidly evolving areflexic motor paralysis with
  or without senosry disturbance
• Usual pattern is ascending paralysis rubbery
  legs
• Weakness evolves over hours to days
• Associated with tingling dysesthesias in the
  extremities
• Legs are usually more affected than the arms

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Clinical Manifestation

• Pain in the neck, shoulder, back or diffusely
  over the spine is common in the early stages
• Most patients require hospitalization and 30
  require mechanical ventilation
• Bladder dysfunction may occur in severe cases
• Once clinical worsening stops and reaches a
  plateau (almost always within 4 weeks of onset),
  further progression is unlikely

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Antecedent Events

• Approximately 70 occur 1-3 weeks after an acute
  infectious process, usually respiratory or
  gastrointestinal
• Organisms that may be responsible
• Campylobacter jejuni
• CMV or Epstein barr virus
• Mycoplasma pneumoniae

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Immunopathogenesis

• Acute inflammatory demyelinating polyneuropathy
  (AIDP) most common type of GBS
• Both CMI and humoral immunity contribute to
  tissue damage
• Antibodies to gangliosides

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Subtypes of GBS

• AIDP
• Rapid recovery, anti-GM1 antibodies
• Acute Motor axonal neuropathy (AMAN)
• Anti GD1a antibodies
• Acute Motor sensory anxonal neuropathy (AMSAN)
• Recovery slow
• Miller Fisher syndrome
• Anti GQ1b antibodies

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Pathophysiology

• In the demyelinating forms of GBS, the basis for
  flaccid paralysis and senosry disturbance is
  conduction block, axonal connections remain
  intact

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Laboratory Features

• CFS findings
• Elevated CSF protein
• Without accompanying pleocytosis
• Csf is often normal when symptoms have been
  present for lt48 hrs

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Diagnosis

• Diagnosis is made by recognizing the pattern of
  rapidly evolving paralysis with areflexia,
  absence of systemic symptoms and characteristic
  antecedent events
• Required diagnostic criteria
• Progressive weakness of 2 or more limbs due to
  neuropathy
• Areflexia
• Disease course lt 4 weeks
• Exclusion of other causes

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Treatment

• Treatment should be initiated as soon after the
  diagnosis as possible
• 2 weeks after the first motor symptoms,
  immunotherapy is no longer effective
• IVIg (2g/kg) or plasmapheresis (40-50 ml/kg
  plasma exchange 4x/week)

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Prognosis

• Approximately 85 of patients with GBS achieve
  full functional recovery within several months to
  a year
• Mortality rate is lt5 in optimal settings
• Death usually result from secondary pulmonary
  complications