Mechanism of Viral Infection and Pathogenesis

Question 1

Why don’t most viruses infect us

Answer 1

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

Question 2

Sites of Microbe Entry - list 9

Answer 2

Conjunctiva

Arthropod

Capillary

Respiratory Tract

Scratch, injury

Alimentary tract

Urinogenital tract

Skin

Anus

Question 3

Common virus diseases of man - list 13

Answer 3

Influenza			
Common cold		Poliomyelitis
Measles				
Mumps
Chicken pox/Shingles
Glandular fever
Hepatitis
Papillomas (Warts)
AIDS
Kaposi’s sarcoma
COVID-19?
Smallpox

Question 4

HHV-1 - define

Answer 4

Herpes virus that causes cold sores and fever blisters in and around the mouth.

rarely (immune system = severely compromised) = infection of the brain (encephalitis)

Question 5

HHV-3 - define

Answer 5

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)

Question 6

Describe transport of herpes into nucleus + amplification

Answer 6

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

Question 7

Examples of persistent infections

Answer 7

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

Question 8

How does virus infection of a host lead to disease?

Answer 8

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

Question 9

Inapparent Infections require viruses to be what

Answer 9

Requires that viruses be non-cytopathic and host-adapted

Question 10

How does virus infection of a host lead to disease?

Answer 10

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

Question 11

Describe negative impact of immune system in relation to pathogenesis of viruses

Answer 11

On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)

Question 12

Chronic hepatitis - define

Answer 12

Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection

HCV is non-cytopathic

Question 13

Chronic hepatitis - associated with what

Answer 13

Hepatitis associated with extensive liver infiltration of leukocytes

Question 14

Chronic hepatitis - cytokine levels

Answer 14

Pro-inflammatory cytokine levels very high

Question 15

Chronic hepatitis - association of viral clearance

Answer 15

Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them

Question 16

Chronic hepatitis - persistence associated with

Answer 16

HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells

Question 17

Dengue virus - define

Answer 17

Dengue virus infection is the most common mosquito-borne infection worldwide – even surpassing malaria

Question 18

Dengue virus - types

Answer 18

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

Question 19

Dengue virus - negative effects of antibodies

Answer 19

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

Question 20

Dengue virus - role of non-neutralizing antibodies

Answer 20

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

Question 21

Influenza - pathology

Answer 21

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

Question 22

The outcome of an infection depends on

Answer 22

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