Mechanism of Viral Infection and Pathogenesis Flashcards
Why don’t most viruses infect us
They are adapted to non-human hosts
They are excluded by surface barriers
Innate Immunity prevents them establishing
Our adaptive immune response has seen something similar
Sites of Microbe Entry - list 9
Conjunctiva
Arthropod
Capillary
Respiratory Tract
Scratch, injury
Alimentary tract
Urinogenital tract
Skin
Anus
Common virus diseases of man - list 13
Influenza Common cold Poliomyelitis Measles Mumps Chicken pox/Shingles Glandular fever Hepatitis Papillomas (Warts) AIDS Kaposi’s sarcoma COVID-19? Smallpox
HHV-1 - define
Herpes virus that causes cold sores and fever blisters in and around the mouth.
rarely (immune system = severely compromised) = infection of the brain (encephalitis)
HHV-3 - define
Human alphaherpesvirus 3 (HHV-3), usually referred to as the varicella-zoster virus (VZV), is one of nine herpesviruses known to infect humans. It causes chickenpox (varicella)
Describe transport of herpes into nucleus + amplification
Retrograde axonal transport involving microtubules to neuronal nucleus
Each nucleus contains more than one copy, amplification probably occurs using host cell machinery - host dependent origin of replication - episomal
Examples of persistent infections
HIV; Virus infects CD4+ cells and weakens immune system
HCV; Virus infects hepatocytes and damages liver
Congenital Rubella; if infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate (and cause damage) in neonatal tissues
How does virus infection of a host lead to disease?
Many infections are apathogenic or associated with relatively mild symptoms; it is important to realize that from the virus’ point of view these are not always failed or resolved infections – a successful virus is one that replicates well enough to spread to the next host
Inapparent Infections require viruses to be what
Requires that viruses be non-cytopathic and host-adapted
How does virus infection of a host lead to disease?
Pathogenesis results from cell and tissue damage caused by the viral infection. On most occasions the damage is limited by the host’s immune system
Describe negative impact of immune system in relation to pathogenesis of viruses
On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)
Chronic hepatitis - define
Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
HCV is non-cytopathic
Chronic hepatitis - associated with what
Hepatitis associated with extensive liver infiltration of leukocytes
Chronic hepatitis - cytokine levels
Pro-inflammatory cytokine levels very high
Chronic hepatitis - association of viral clearance
Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
Chronic hepatitis - persistence associated with
HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells
Dengue virus - define
Dengue virus infection is the most common mosquito-borne infection worldwide – even surpassing malaria
Dengue virus - types
There are 4 serotypes (1–4), all of which have the same clinical manifestations:
acute fever severe abdominal pain headache Plasma leakage Intravascular vol depletion Coagulation dysfunction
Dengue virus - negative effects of antibodies
Antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus. In fact they may result in more severe disease due to a phenomenon known as antibody-dependent enhancement or ADE
Dengue virus - role of non-neutralizing antibodies
Non-neutralizing antibodies coat virus, forming immune complexes which get internalised into mononuclear phagocytes through their Fc receptors;
fixation of complement by circulating immune complexes results in release of products of the complement cascade leading to sudden increased vascular permeability, shock and death
Influenza - pathology
Pathology:
Mild URTI to severe LRTI Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia Fever, often prolonged Neurological (headache, malaise) Myalgia
The outcome of an infection depends on
The outcome of an infection depends on what you are infected by, the route of infection, whether you’ve seen it (or anything like it) before, and the state of your immune system
