Virus-Host Interaction & Pathogenesis Flashcards
Susceptibility factors maintaining viral diseases:
* _________ of viral virulence
* _________ of viral virulence
* Determination of host ________
* Factors affecting virus/host ______/______
Assessment, Determination, susceptibility, resistance, susceptibility
Mechanisms of viral infections and viral dissemination
* Routes of viral ____
* Host ______ and tissue _____
* Methods of viral _______/_____ inside the host
entry, specificity, tropism, dissemination, spread
Mechanisms of viral spread and infection of target organs
* Types of virus-cell ______
* Virus mediated tissue organ _____
interactions, injury
Virus induced tumour
- RNA viruses induced oncogenesis
- DNA viruses induced oncogenesis
Viral pathogenesis is defined as the process by which a viral infection leads to _____.
disease
The outcomes of the viral infections depends on the interplay between some ____ and ____ factors
viral, host
Factors affecting viral pathogenesis:
1. Effects of viral infections on ____ (?)
2. Entry into the ____
3. _____ of the infection ( _____ replication, _____ spread & ______ replication).
-Cell/tissue _____
-Cell/tissue _____
- _____ immune response
-Virus _______ or ______
cells, Cellular Pathogenesis, Host, Course, primary, secondary, tropism, damage, host, clearance, persistence
Virulent virus: relevant term to measure the ability of the virus to ______ ______ in a particular host
induce disease
Factors affecting the viral virulence:
-Ability of he virus to ____ and ____ in a particular host
- Virus must have the ability to ____ the host
-Virus has the ability to ____ the host immune response
- Virus is able to cause ______ in the target host
grow, multiply, invade, evade, damage
Viral virulence is based on some viral/host related factors
- Age, gender, immune status
-Virus concentration
Permissive cells are cells that ?
support viral replication (receptors, co/receptors, transcription, translation
factors)
Non-permissive cells are defined as ?
cells in which viral infection can not be established
Mechanisms of viral induced diseases in the affected host
Steps of viral replication in the host
Essential steps in the viral
infections/requirement for viral
survival and progression of infection
Types of viral infections - Productive
Productive
-Virus introduced its
genome into the cells
-New viral progeny
are made
Types of viral infections - Latent
-Viral genome is
incorporated into the
host cell genome
-Production of
infectious virus does not
occur immediately
Productive infection
occur latter on
Types of viral infections - Abortive
Virus initiated the
infection
- No viral progeny
produced
Types of viral infections - Persistent
Long term viral infection
when the immune system
failed to clear acute viral
infection
Recrudescence: a new outbreak after a period of ______ or ______.
abatement, inactivity
Types of viral infections with reference to viral load and timeline
Recurrent: repeated cycle of viral infection. Recover a little bit, then feel sick again b/c you do not have complete clearance.
Types of viral infections - Lytic infection
Destruction of cells at greater
rates than they may be
replaced
Ex: Pseudorabies virus: CNS cells
Ex: ICHV: liver cells
Types of viral infections - Latent infection
-Viral genome incorporated into
the host cell genome with no
synthesis of viral proteins until
animals exposed to stress
conditions thus the viral
replication will be activated
Ex: Herpesvirus infection in
neurons and ganglions
Ex-2: Reovirus in lymphocytes
Types of viral infections - Persistent infecton
-BVDV: Intrauterine infection
of foetus during mid stage of
pregnancy results in immune
tolerant calves
-Calves shed the virus either
continuously or intermittently
acting as source of infection to
other animals
Types of viral infections - Immune complex disease
-EIAV: Abs may cause
immunopathologic conditions
Abs combines with virus to
cause immune complex
deposited in the glomeruli in
the kidney and in organs
causing inflammation
Shedding of the virus and the occurrence of the clinical signs in acute-self limiting
infections in various kinds of persistent
infection
Typical curve of acute viral infection
Entry of virus
Incubation period = no clinical signs
Patterns of viral infection
* Acute infection followed by viral _____
* Acute infection but ‘______’ tissue infected with ______ damage despite viral clearance
* ______ infection: latent, slow, transforming
* ____ incubations
clearance, accidental, permanent, Persistent, Long
Ex: Influenza virus, Rhinovirus, Rotavirus, Coronavirus
Patterns of viral infection
Patterns of viral infection
Viral persistence is defined as?
Viral persistence: the inability of the immune system to clear an acute viral infection
Causes of viral persistence
-Immunodeficiency due to HIV infection
-Transplant
-Chemotherapy
-Genetic conditions
-Congenital infections (BVDV)
Outcomes of the persistent viral infections
- No apparent effects (Polyomavirus, Herpesvirus)
-Chronic or progressive infections (measles, chronic hepatitis)
-Cancer
-Clinical reactivation (Genital herpesvirus infection)
Significance of persistent infections
Maintenance of virus in animal population
Mechanisms of viral persistence
Viral evasion to the host innate immune response
* Modulation of the adaptive immune system
* Induction of latency
* Infection of tissues not readily accessible to the immune system such as keratinocytes
* Immune response escape mutants: HBCV, HIV
* Prolonged survival of the infected cell (oncogene)
Mechanism of Herpesvirus reactivation
Routes of viral infection - Respiratory tract
-Inhalation of droplet nuclei of 1-10
cause infection
-1-3 um droplets penetrates into
bronchioles
-Resp tract defense
Mucociliary clearance
Phagocytosis by alveolar macrophages
in lung
-Influenza virus produce
neuraminidase liquefy mucous
Routes of viral infection - Skin
-Intact skin act as impermeable
barrier against viruses but can be
breached by
-insect bites (BTV, EEEV)
-Animal bites (Rabies)
-Contaminated instruments (EIAV)
Routes of viral infection - Genital tract
-Venereal infection is rare in animals
-BHV-1 transmitted by venereal routes
EHV-3 causes coital exanthema in
horses
Routes of viral infection - alimentary tract
-Virus ingested with food and water or
licking contaminated objects
-Low pH of stomach and high pH of
intestine inactivates some viruses
-Digestive tract protected by layer of
mucous
-Peristaltic action helps to remove
viruses
Routes of viral infection - Placenta
-Viremia in pregnant female the virus
may cross the placenta and infect foetus
-Killed foetus resulted in
A- infertility
B-Mummified foetus
C-Abortion
D- Stillbirth
-Survived foetus may be congenital
anomalies
Routes of viral infection - genital tract
-Venereal infection is rare in animals
-BHV-1 transmitted by venereal routes
EHV-3 causes coital exanthema in
horses
Routes of viral infection - conjunctiva
IBRV conjunctival form
Viral entry/spread- through respiratory epithelium
Respiratory tract: the respiratory tract and all other mucosal surfaces possess sophisticated
immune defense mechanisms, as well as non-specific inhibitory mechanisms
(ciliated epithelium, mucus secretion, lower temperature) which viruses must overcome
Respiratory tract is protected by
Respiratory tract is protected by
1- The mucous blanket
2-The beating of the ciliated epithelium
Influenza
* IBRV (Infectious bovine rhinotracheitis)
* Common Cold (Rhino, Adeno, Corona) viruses
* Parainfluenza Virus
* Respiratory syncytial virus (RSV)
SEM pictures of
Rhinovirus infection
in trachea
A: Normal trachea showing the ‘’carpet’’
* B: Trachea of Rhinovirus infection: only
some tufts of the epithelium are showing
(loss of the carpet appearance
Pathogenesis of ectromelia (mousepox) virus
Pathogenesis of ectromelia (mousepox) virus
Viral invasion to the sub-epithelial layers and lymphatic spread
Virus damages epithelial linining to ente rlymphatic vessels –> lymph nodes –> blood stream
Droplet infection: an infection transmitted
from one individual to another by droplets
of moisture expelled from the ______ _______ ____ through ______ or _____
upper respiratory tract, sneezing, coughing
Aerosol: Aerosol Transmissible Diseases
Aerosol transmissible diseases (ATDs), such as _____, are transmitted by infectious ______ or ______ through ______ or _____ contact with ______ membranes in the ______ tract or ____
measles, particles, droplets, inhalation, direct, mucous, respiratory, eyes
- Fomite: or environmental surfaces
- (1) Clinical contact surfaces such as dental
units, x-ray machines, equipment knobs, etc - (2) Housekeeping surfaces
Mechanisms of viral infection,
spread, shedding, and
transmission to other hosts
Roles of viremia in the
spread of viruses through
the body
* Indicating sites of
replication and important
roles of shedding of
various viruses
Viral entry through skin
Skin: most viruses which infect via the skin require a breach in the _____ integrity of this effective barrier, e.g.
cuts or abrasions Keratin
physical
Replication of papillomavirus in skin
Shingles: viral disease characterized by a _____ ____ ___ with _____ in a _____ area
* Infection through the ________ and _____ ______ tract
* Replication in the _______ ______ _____
* Primary viremia
* Replication in ____, _____, and ____
* Secondary viremia
* Infection of the ____ and appearance of _____ _____
* Infection of ______ _____ and establishment of _____ infection
painful skin rash, blisters, conjunctiva, upper respiratory, primary lymph nodes, liver, spleen, other, skin, skin rashes, sensory ganglia, latent
Routes of viral invasion of the central nervous system
Transmission of Rabies virus
Viral replication and spread through nerves
Retrograde
Viral replication and spread through nerves
Anteretrograde
Rabies virus and pseudorabies
cross the ?
synaptic junctions
Retrograde infection : spread of
virus from the ______ terminals to
the neuronal _____ ____ and is
directionally _______ to
movement of the nerve impulse
axon, cell body, opposite
Anterograde neuronal: spread
from the neuron ___ ___ toward
the _____ terminus.
cell body, axon
Local viral spread at mucosal surfaces
Damage of
basement membrane
infection of
underlying cells
Systemic spread of viruses
P: the time between the entrance of the virus into the body of the infected host and the appearance of the
clinical signs
Duration of the IP varies from
-Few days: respiratory viruses such as Influenza virus
-Several weeks or months: Maedi-visinia virus and Rabies virus
The systemic infection occurs in the following pattern:
1- The virus multiply at the site of entry and in the lymph nodes- resulting in primary viremia
2- The virus reaches the target organs through secondary viremia and multiplies resulting in cell damage resulting
in diseases development
Shingles Pathogenesis:
-Virus reach skin via blood stream to produce generalized ____ ____
-Virus spread to brain via ______ ______ ______ or _______ nerves as in case of rabies virus
-_____ _____ transmission may occur in pregnant animals in some viruses as BVDV, BTV
skin rashes, cerebellar blood vessels, peripheral, Trans placental
Mecahnism of viral spread:
virus enters through nasal tract, oropharynx, ornany other mucosa. Infects cells, then enihboring lymph nodes –> primary and secondary –> target organ
Viruses that cause systemic infection and spread via blood must be able to
infect or replicate and/or survive in _____ and ______
lymphocytes, macrophages
Sub-epithelial invasion an lymphatic spread of viral infections
Virus enters epithelial surface, subepithelial –> MQ goes to DC –> Lymph nodes –> Efferent lymphatic vessel –> Vena cava –>blood -> circulates throughout body.
Virus may be amplified in the ______ or infect ?
epithelium, sub epithelial macrophages
Cell-free virus or infected macrophages/dendirtic cells pass to regional lymph node via ?
afferent lymphatic
Viral progeny released into venous secretions to cause _____ which may be cell ___ or cell ______
viremia, free, associated
Viral spread through the lymphatics and blood
Transmission of rabies virus
Wild animal bites dog, virus is secreted into blood of animal. Virus penetrares muscle and enters nerve ending and travels to the brain. Rabies travels via nerve endings.
Innoculated virus moves in nerve tissue, not blood.
Virus shedding
Shedding of the virus from the infected animals maintain the circulation of the virus in certain animal
population
* Shedding of the virus usually occur from the same route of virus entry
Skin: shed the virus and can transmit directly via _____ or _____ to another animal
Ex: ?
abrasion, wounds, Cow poxvirus, sheep poxvirus, Marek’s diseases virus
Respiratory tract: virus expelled during _____ and _____
- _____ droplets which fall on several objects
- _____ droplets remains airborne
-Shedding occur from both ___ and ____ secretions then virus spread from infected to susceptible animals
coughing, sneezing, Large, Small, oral, nasal
Alimentary tract: enteric viruses shed in the ____. These viruses are resistant to ?
feces, environmental conditions
Genital tract: shedding in the _____ and ____ secretions during ____ or _____ _______
* Kidney: viruses replicates in the kidneys shed in the ____ of the infected animals
-FMDV and cattle plague virus
semen, genital, coitus, artificial insemination, urine
Blood: arboviruses transmitted by biting of the _____ and contaminated _____
-RVFV, and EIAV
arthropods, needles
Milk: some viruses shed in the ___ as in case of FMDV
milk
Summary
The body surfaces in relation to the virus entry/shedding
Gain access to human body through conjuncativa, scratch/bite, capillaries
Relationship between body surface that routes viral entry
- Local spread from route of entry restricts viral shedding to ? Ex: ?
- Viremic spread from the route of entry results in shedding from ?
- Ex: ?
respiratory secretions, Canine parainfluenza virus, multiple mucosal surfaces, Canine distemper virus infection, includes respiratory mucosa (route of entry) and those of other
organs system, such as urinary tract?
Viral tropism is determined by the followings
-Cell _______ of the virus
-Cell ______ factors that recognize the viral promoters and enhancer sequences
-Ability of the cell to support virus _____
- ______ barriers
-Local ?
- Digestive ______ and ___ in the digestive tract may inactivate some viruses
receptors, transcription, replication, Physical, temperature, pH, and O2 tension enzymes, enzyme, bile
Mechanism of viral tropism
-Cellular receptors _______ expression limits viral entry into specific cell types express the cellular receptors
-Post-entry factors: cell type must be ______ for viral replication
- _______ and ______ machinery compatible with viral life cycle
-Innate-antiviral defenses can be overcome by ?
differential, permissive, Transcription, translation, viral encoded proteins
Classification of viruses according to tissue tropism
Didn’t go into this chart in depth.
Influenza tropism is determined by availability of host proteases
When we are infected by virus, virus is inactive. Once enters host, the presenceof host cell proteases cleaves the heamagluttin from ianctive to active form. Presence of certain proteases –> may contribute to tropism.
Viral determinants of virus survival and transmission
- Viral envelope (if present) and capsid: ______ protein expression and ______
- site of _____
- host receptor binding _____ and ____
- formation of viral _____ - Capsid structure –> virus ______.
- Internal proteins and viral genomes
- ____ packaged –> virus ____
- Polymerase –> host adapted virus ____ - Viral genomes
- Mutations –> host _____
surface, modification, infection, specificity, affinity, aggregates, stability, Densely, stability, replication, adaptation
Outcomes of Infection at Molecular and
Cellular levels (Cellular pathogenesis)
- Cell Death
- Persistent Infection
- Transformation (Hyperplasia)
- Abortive Infection
Cell Death (cytopathic/cytocidal):
By necrosis or apoptosis, usually with production of
daughter virus particles. Most frequent outcome.
Persistent Infection
(No apparent change, non cytocidal /non cytopathic): Constant
production of virus, without cell destruction.
Transformation (Hyperplasia):
Virus may not be produced, depends on the transforming
virus
Abortive Infection
Cell may be damaged, killed, or transformed in some cases, but no
daughter virus is made
Effects of the viruses on the cells
- Cytocidal
- Non-cytocidal
- Transformation
I- Cytocidal
* Highly Cytocidal viruses ceases the cellular ________ synthesis of important _____ leading to rapid _______ of the infected cells
macromolecular, proteins, destruction
Cell death/lysis may arise from?
1. Shut down of cellular ____ and ____ synthesis
2. Accumulation of viral _____ during replication
3. Some capsid proteins are ____ to some cells
4. Viral components accumulates at the site of multiplication forming _______ ____ which distort the cells and increase its _______
- Cellular lysosomal enzymes leak out resulting ______ _____ of the cells
RNA, protein, macromolecules, toxic, inclusion bodies, permeability, autolytic digestion
The _______ effects of the virus on the _______ cells called cytopathic effects called (CPE)
pathological, infected
Mechanism of viral injury to the host
Types of virus/host cell interactions
He discussed:
persistent productive , persistent non productive
Mechanisms of viral disease production
1. _____ damage of the cells result in ______ of the affected organs.
2. The pressure effects of the ____ that results from the ______ exudation and infiltration
3. Secondary ______ invasion facilitated by the presence of destructed ______ cells
4.Damage of the immune system may lead to _______ and ______.
Direct, impairment, edema, inflammatory, bacterial, epithelial, immunodeficiency, immunosuppression
Immune response in some viral infection may cause immune complex which result in _________ & _______ production
inflammation, disease
Damage associated with antibodies:
Antibody enhancement of infection. Antigen-antibody complexes: damages in kidney and joints
-Some viruses express their antigens on the cell surface
-They become target for MAC lysis, ADCC, cytotoxic T cells
Some mechanisms of viral induced cellular injury
Infected some cells with target virus and see several pathologies including cell lysis etc.
Effects of cytocidal viruses on the cells - Cell fusion-Multinucleate giant cells (Syncytia)
*Some enveloped viruses have ______ _____ in envelope
*Upon infection, _____ fusion proteins are translated in cell
*The new fusion proteins are transported to _____ ____ and expressed on cell membrane
*So budding virus can pick up these proteins when picking up envelope from cell membrane
*The viral fusion proteins on cell surface can cause ? –> generates a _______ _____.
* Virus can spread from cell to cell without exiting cell
* Viral fusion proteins are important pathogenic molecules
fusion proteins, new, cell surface, fusion of infected cell with neighboring uninfected cell , multinucleate syncytium
MNGC is an impact of virus in some tissues.
List the effects of cytocidal viruses on cells.
- Cytopathic effects
- Cell fusion-Multinucleate giant cells (Syncytia)
- Inclusion Bodies = Viral Factories (IP)
- Shutdown of cellular macromolecular synthesis
- Release of enzymes by lysosomes
- Expression of viral antigens on cell surfaces of infected cells
- Effects on host cell chromosomes: the highly cytocidal
viruses induce changes in the form of
-Chromosome breaches
-Translocation
-Deletion
Rabies brain stained with
H&E
Line pointing to Negri bodies
Line pointing to negri bodies
Rabies brain stained with
Fluorescent anti-rabies
antibodye
Intra-cytoplasmic
Intranuclear
Herpesvirus
Intranuclear inclusion bodies
Inclusion Bodies (= Viral Factories) (IP)
* IP: viral components accumulated at the site of virus multiplication either in the ____ or in the ____
* IP: may be ___ or ___, ____ or _____
nucleus, cytoplasm, large, small, acidophilic, basophilic
Shutdown of cellular macromolecular synthesis: Most cytocidal viruses code for _____ ____ which stop the
synthesis of cellular ___ proteins
early proteins, RNA
Release of enzymes by lysosomes: Activation of lysosomal enzymes may be important
mechanism of the production of _____ ____ by viruses. The produced lysosomes increase the ______ of the
membranes and they diffuse ___ of the cell
cellular damage, permeability, out
Expression of viral antigens on cell surfaces of infected cells: Some viruses expressed some of their proteins (______) on the plasma membranes of the infected cells
Ex: ?
peplomers, Influenza virus express hemagglutinin on the cell surface of
infected cells
Effects on host cell chromosomes: the highly cytocidal viruses induce changes in the form of
- ________ breaches
- ______
- _______
Chromosome, Translocation, Deletion
- What can be seen in the image below?
- What is this an example of?
1.BVD Negative control
2. Example of non cytopathic bovine viral diarrhea virus (BVD), retroviruses
- What can be seen in the image below?
- What is this an example of?
- Immunohistochemical staining of BVD antigen ear notch
- Example of non cytopathic bovine viral diarrhea virus (BVD), retroviruses
- What can be seen in the image below?
- What is this an example of?
- FA staining showing BVD antigen
- Example of non cytopathic bovine viral diarrhea virus (BVD), retroviruses
Viral oncogene: a viral gene that transform a ______ cell into _____ cells which can grow and multiply _______. Viral oncogenes derived from the ____ cell genes then incorporated into the ____ genome then induce _____. Viral oncogenes interfere with the host cell ____ and ______ genes. Host cells lose the ____ control ability thus continue to multiply _______.
normal, cancer, indefinitely, host, viral, mutations, growth, multiplication, division, indefinitely
How did scientists utilize the Rouce sarcoma virus for cancer research?
Cytocidal viruses can stimulate cell growth ds DNA viruses.
Retro viruses encode trans-activating genes that increases gene expression of cellular genes involved in cell cycle regulation , RNA virus (BLV)
- What can be seen in the image below?
- What type of virus is this?
- BLV-induced malignant lymphoma in abomasum
- RNA virus
- What can be seen in the image below?
- What type of virus is this?
- BLV-induced malignant lymphoma in the adrenal gland
- RNA virus
- What can be seen in the image below?
- What type of virus is this?
- Marek’s Disease; CD4+ T cell Lymphoma
- DNA virus
- The viral ________ play(s) a role in attaching a virion to the host cell.
a. envelope
b. capsid
c. core
d. both a and b
d
- Which statement/s are true about the viral shapes
a. all have a round shape
b. cannot have a long shape
c. do not maintain any shape
d. vary in shape
d
- Which statement is true of reverse transcriptase?
a. It is a nucleic acid.
b. It infects cells.
c. It transcribes RNA to make DNA.
d. It is a lipid.
c
