viral infections: an overview
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Viral Infections: an overview. Dr. Gerrard Uy. 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 - PowerPoint PPT PresentationTRANSCRIPT
Viral Infections: an overview
Dr. Gerrard Uy
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
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
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
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
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 3–4 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
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
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
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
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 sarcoma–associated herpesvirus (KSHV, also known as HHV-8)].
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
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
Resistance to Viral Infections
• By 7–10 days after infection, virus-specific antibody responses develop
• virus-specific HLA class II–restricted CD4+ helper T lymphocyte responses, and virus-specific HLA class I–restricted CD8+ cytotoxic T lymphocyte responses• Antibody and complement can also lyse virus-infected
cells that express viral proteins on their surface
• host inflammatory and immune response contributes to the symptoms, signs, and other pathophysiologic manifestations of viral infection
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
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
• 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.
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
Immunization
• Smallpox• Poliovirus• Measles• Influenza• Chickenpox• HBV• Mumps, rubella
Guillain-Barre Syndrome
Guillain-Barre Syndrome
• Acute, frequently severe, and fulminant polyradiculopathy
• Autoimmune in anture• Males have higher risk than females
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
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
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
Immunopathogenesis
• Acute inflammatory demyelinating polyneuropathy (AIDP) – most common type of GBS
• Both CMI and humoral immunity contribute to tissue damage
• Antibodies to gangliosides
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
Pathophysiology
• In the demyelinating forms of GBS, the basis for flaccid paralysis and senosry disturbance is conduction block, axonal connections remain intact
Laboratory Features
• CFS findings:– Elevated CSF protein– Without accompanying pleocytosis– Csf is often normal when symptoms have been
present for <48 hrs
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 < 4 weeks– Exclusion of other causes
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)
Prognosis
• Approximately 85% of patients with GBS achieve full functional recovery within several months to a year
• Mortality rate is <5% in optimal settings• Death usually result from secondary
pulmonary complications