VIRO3002 NOTES
Lecture 2 VIRUSES AS PATHOGENS
• Basic definitions of pathogen, pathogenesis, virulence
• Common overall strategies to viral infection as virus MUST breach
host barriers to enter. Usual portals like skin, resp, GUT, GIT,
conjunctiva
• Viruses that penetrate the skin, method (insect, animal, trauma,
injection). Arbovirus for insect, rabies for animal. Others like HPV,
HSV, HIV
• Viruses penetrate resp tract and cause a LOCALISED infection (inhale
viruses as aerosolised droplets – RSV, influenza, rhinovirus) OR can
DISSEMINATE following asymp initial infection (e.g. chickenpox,
mumps, measles). Divide into serious and non-serious resp viruses.
Lots of host physical defences here.
• Viruses invade the GIT via Faecal-Oral route or eating/drinking.
Localised (rotavirus, norovirus) or systemic (enterovirus, hep A,
poliovirus that spread out from GIT). Lots of hostile host defences.
• Viruses invade the GUT via infection through sexual activity. Few
different methods – can enter through tears/abrasion in lining (HIV), or
infect epithelium (HPV – local lesions), or infect underlying tissues
(sensory neurons HSV, even during birth, or lymphoid tissue HIV). Lots
of host defences like low pH (vagina), mucous layer and macrophages.
• Viruses invade the conjunctiva via abrasion or poor sanitation. Can
cause localised infections e.g. conjunctivitis, or spread to other sites
like HSV-1. Lots of host physical defences.
• Once breached host barriers, viruses can cause LOCALISED or
DISSEMINATED or SYSTEMIC infection.
• In localised, just replicate at primary infection site and spread to
adjacent cells.
• In disseminated, must breach physical and immunological barriers
and spread to other organs/tissues via CIRC or NERVOUS SYSTEM.
• Systemic is a severe version of disseminated, many organs affected,
common if have immune impairment. In both disseminated and
systemic, viruses move to their PREFERRED site of replication e.g.
poliovirus.
• Common localised infections = resp (influenza, rhinovirus), GIT (rotavirus),
skin infections (HPV).
• Viruses can disseminate by circ system – enter capillaries via
bite/puncture, move through blood in cells, subvert cell functions e.g.
HIV in T cells/monocytes or EBV in B cells or measles in monocytes of
, VZV in T cells.
• Viruses can disseminate via the nervous system = enter Dorsal Root
Ganglia or motor nerve ending.
• Neurons ideal because post-mitotic and immune privileged. E.g.
Rabies, poliovirus, HSV (sensory) or VZV.
• Innate Immune Response = first line = skin, mucous membrane,
gastric juice. All PASSIVE. Not normal flora because not bacterial
infection.
• Innate Immune Response = second line = NK, macros, eosinophils, cytokines.
Needs to be activated, 24 hrs.
• Adaptive Immune Response = third line = T cells, B cells, Ab. Needs to be
activated, several days.
•
• Types of infection: acute is easily cleared but not persistent e.g.
localised infections, rotavirus or influenzavirus. If persistent chronic,
virus continues to be produced at low levels then reignites at immune
tipping point e.g. HIV or measles. If persistent latent, only viral genome
remains have
restricted gene expression, reawakens periodically when
immunosuppressed with or without symptoms e.g. herpesviruses.
• Virus shedding = release of infectious virus from the host. Can be Transmitted
via aerosols (cough, sneeze
e.g. influenzavirus, SARS coronavirus) Faecal-Oral route (vomit,
diarrhoea, food, objects, water e.g. rotavirus, hep A and E, poliovirus,
norovirus), skin lesions (cold sore or genital herpes e.g. HSV), blood
(needles, birth, insect bite, sexual activity e.g. WNV, Dengue, Hep C,
HIV) or body fluids (breast milk CMV, urine hantavirus, semen
HIV/CMV/Hep B).
• The success of shedding depends on:
o number of infectious virus shed,
o stability of virus in environment (envelope reduces
stability)
o number of virus required to infect a new host (depends
on virus and route of Transmission)
• Routes of Transmission can be divided into horizontal, vertical and
zoonoses.
o Horizontal means between humans e.g. aerosol, FOR or sexual
contact.
o Vertical also means between humans but mother to child –
e.g. prenatal (transplacental) CMV/HIV, perinatal (infected
, birth canal) e.g. Hep B or HSV, or postnatal (milk or direct
contact) CMV, Hep B.
o Zoonoses means bite from animals e.g. arthropods or animals
– effectively H2H but animal intermediate.
o
• Some features of virus infection lead to symptoms of disease e.g.
cytolysis, apoptotic response, loss of cell function, transformation of
cells to become a tumour.
• BUT host factors also influence viral pathogenesis e.g.
immunopathology (Antibody or immune cell mediated tissue
damage) or inflammation (swelling, rash).
Acute infection
• Rapid production and transmittance of infection virions
• Rapid resolution of infection – not even genome remaining. All virions
and infected cells cleared.
• Usually brief in ImmunoCompetent individuals.
• E.g. rotavirus, influenzavirus, rhinovirus (all localised virus infections as
easier to clear).
Persistent latent infection
• Result from ineffective clearance of acute infection
(immunocompromised or particularly nasty virus) – virus particles
continue to be produced for long periods
• After initial acute infection, infectious virus is cleared, but viral genome
persists (no intact virions or infectious virus). Restricted gene expression
and non-replicating form.
• Typical of herpesviruses – hide in immunoprivileged sites e.g. HSV.
• Virus re-awakens periodically, e.g. if immunosuppressed, via
‘reactivation’. This can be SYMP or ASYMP reactivation.
, Persistent chronic
infection
• Result from ineffective clearance of acute infection
(immunocompromised or particularly nasty virus) – virus particles
continue to be produced for long periods
• Pattern initially mimics acute infection, but virus not completely
eliminated – infectious virus produced at very low levels
• See increase and symptoms at immune tipping point
• E.g. HIV or measles
L3 KF: VIRAL RECEPTORS
• The cell membrane is covered with structures (integral and membrane-
associated), and glycoproteins can act as ligands to viral proteins
(receptors) though this isn’t their main function. The membrane is thick
and protective.
• Entry can be pH-dependent or pH-dependent. It doesn’t matter where
the acid comes into play (doesn’t have to allow uncoating), but just
needs to be relevant to the path between entry and uncoating.
• Uncoating refers to the release of viral GENOME (loss of capsid).
This can occur at the plasma membrane, within endosomes, OR at
the nuclear membrane = three potential sites.
• An enveloped virus can fuse with the plasma membrane OR be
internalised into an endosome, but an unenveloped virus cannot fuse
with the membrane, and must be internalised into an endosome.
Both endosomal actions are pH dependent, but one involves
endosome destruction (non-env virus) and one does not (env virus).
• An enveloped virus can:
o Fuse with the cell membrane and uncoat
immediately = pH independent = paramyxovirus,
HIV.
o Fuse with the CM but retain capsid until dock onto nuclear
membrane, where it uncoats = pH independent = herpesvirus.
o Become endocytosed (two membrane away from host
cytoplasm) an fuse its envelope with the endosomal
membrane via a pH-dependent reaction (does not damage
endosome), allowing uncoating = influenzavirus
• An unenveloped virus can:
Lecture 2 VIRUSES AS PATHOGENS
• Basic definitions of pathogen, pathogenesis, virulence
• Common overall strategies to viral infection as virus MUST breach
host barriers to enter. Usual portals like skin, resp, GUT, GIT,
conjunctiva
• Viruses that penetrate the skin, method (insect, animal, trauma,
injection). Arbovirus for insect, rabies for animal. Others like HPV,
HSV, HIV
• Viruses penetrate resp tract and cause a LOCALISED infection (inhale
viruses as aerosolised droplets – RSV, influenza, rhinovirus) OR can
DISSEMINATE following asymp initial infection (e.g. chickenpox,
mumps, measles). Divide into serious and non-serious resp viruses.
Lots of host physical defences here.
• Viruses invade the GIT via Faecal-Oral route or eating/drinking.
Localised (rotavirus, norovirus) or systemic (enterovirus, hep A,
poliovirus that spread out from GIT). Lots of hostile host defences.
• Viruses invade the GUT via infection through sexual activity. Few
different methods – can enter through tears/abrasion in lining (HIV), or
infect epithelium (HPV – local lesions), or infect underlying tissues
(sensory neurons HSV, even during birth, or lymphoid tissue HIV). Lots
of host defences like low pH (vagina), mucous layer and macrophages.
• Viruses invade the conjunctiva via abrasion or poor sanitation. Can
cause localised infections e.g. conjunctivitis, or spread to other sites
like HSV-1. Lots of host physical defences.
• Once breached host barriers, viruses can cause LOCALISED or
DISSEMINATED or SYSTEMIC infection.
• In localised, just replicate at primary infection site and spread to
adjacent cells.
• In disseminated, must breach physical and immunological barriers
and spread to other organs/tissues via CIRC or NERVOUS SYSTEM.
• Systemic is a severe version of disseminated, many organs affected,
common if have immune impairment. In both disseminated and
systemic, viruses move to their PREFERRED site of replication e.g.
poliovirus.
• Common localised infections = resp (influenza, rhinovirus), GIT (rotavirus),
skin infections (HPV).
• Viruses can disseminate by circ system – enter capillaries via
bite/puncture, move through blood in cells, subvert cell functions e.g.
HIV in T cells/monocytes or EBV in B cells or measles in monocytes of
, VZV in T cells.
• Viruses can disseminate via the nervous system = enter Dorsal Root
Ganglia or motor nerve ending.
• Neurons ideal because post-mitotic and immune privileged. E.g.
Rabies, poliovirus, HSV (sensory) or VZV.
• Innate Immune Response = first line = skin, mucous membrane,
gastric juice. All PASSIVE. Not normal flora because not bacterial
infection.
• Innate Immune Response = second line = NK, macros, eosinophils, cytokines.
Needs to be activated, 24 hrs.
• Adaptive Immune Response = third line = T cells, B cells, Ab. Needs to be
activated, several days.
•
• Types of infection: acute is easily cleared but not persistent e.g.
localised infections, rotavirus or influenzavirus. If persistent chronic,
virus continues to be produced at low levels then reignites at immune
tipping point e.g. HIV or measles. If persistent latent, only viral genome
remains have
restricted gene expression, reawakens periodically when
immunosuppressed with or without symptoms e.g. herpesviruses.
• Virus shedding = release of infectious virus from the host. Can be Transmitted
via aerosols (cough, sneeze
e.g. influenzavirus, SARS coronavirus) Faecal-Oral route (vomit,
diarrhoea, food, objects, water e.g. rotavirus, hep A and E, poliovirus,
norovirus), skin lesions (cold sore or genital herpes e.g. HSV), blood
(needles, birth, insect bite, sexual activity e.g. WNV, Dengue, Hep C,
HIV) or body fluids (breast milk CMV, urine hantavirus, semen
HIV/CMV/Hep B).
• The success of shedding depends on:
o number of infectious virus shed,
o stability of virus in environment (envelope reduces
stability)
o number of virus required to infect a new host (depends
on virus and route of Transmission)
• Routes of Transmission can be divided into horizontal, vertical and
zoonoses.
o Horizontal means between humans e.g. aerosol, FOR or sexual
contact.
o Vertical also means between humans but mother to child –
e.g. prenatal (transplacental) CMV/HIV, perinatal (infected
, birth canal) e.g. Hep B or HSV, or postnatal (milk or direct
contact) CMV, Hep B.
o Zoonoses means bite from animals e.g. arthropods or animals
– effectively H2H but animal intermediate.
o
• Some features of virus infection lead to symptoms of disease e.g.
cytolysis, apoptotic response, loss of cell function, transformation of
cells to become a tumour.
• BUT host factors also influence viral pathogenesis e.g.
immunopathology (Antibody or immune cell mediated tissue
damage) or inflammation (swelling, rash).
Acute infection
• Rapid production and transmittance of infection virions
• Rapid resolution of infection – not even genome remaining. All virions
and infected cells cleared.
• Usually brief in ImmunoCompetent individuals.
• E.g. rotavirus, influenzavirus, rhinovirus (all localised virus infections as
easier to clear).
Persistent latent infection
• Result from ineffective clearance of acute infection
(immunocompromised or particularly nasty virus) – virus particles
continue to be produced for long periods
• After initial acute infection, infectious virus is cleared, but viral genome
persists (no intact virions or infectious virus). Restricted gene expression
and non-replicating form.
• Typical of herpesviruses – hide in immunoprivileged sites e.g. HSV.
• Virus re-awakens periodically, e.g. if immunosuppressed, via
‘reactivation’. This can be SYMP or ASYMP reactivation.
, Persistent chronic
infection
• Result from ineffective clearance of acute infection
(immunocompromised or particularly nasty virus) – virus particles
continue to be produced for long periods
• Pattern initially mimics acute infection, but virus not completely
eliminated – infectious virus produced at very low levels
• See increase and symptoms at immune tipping point
• E.g. HIV or measles
L3 KF: VIRAL RECEPTORS
• The cell membrane is covered with structures (integral and membrane-
associated), and glycoproteins can act as ligands to viral proteins
(receptors) though this isn’t their main function. The membrane is thick
and protective.
• Entry can be pH-dependent or pH-dependent. It doesn’t matter where
the acid comes into play (doesn’t have to allow uncoating), but just
needs to be relevant to the path between entry and uncoating.
• Uncoating refers to the release of viral GENOME (loss of capsid).
This can occur at the plasma membrane, within endosomes, OR at
the nuclear membrane = three potential sites.
• An enveloped virus can fuse with the plasma membrane OR be
internalised into an endosome, but an unenveloped virus cannot fuse
with the membrane, and must be internalised into an endosome.
Both endosomal actions are pH dependent, but one involves
endosome destruction (non-env virus) and one does not (env virus).
• An enveloped virus can:
o Fuse with the cell membrane and uncoat
immediately = pH independent = paramyxovirus,
HIV.
o Fuse with the CM but retain capsid until dock onto nuclear
membrane, where it uncoats = pH independent = herpesvirus.
o Become endocytosed (two membrane away from host
cytoplasm) an fuse its envelope with the endosomal
membrane via a pH-dependent reaction (does not damage
endosome), allowing uncoating = influenzavirus
• An unenveloped virus can:
