HOST AND VIRUS INTERACTION

1. UNIT II
HOST AND
VIRUS
INTERACTION
rambahadurkhadka00@gmail.
com

2. INTRODUCTION
 An appreciation of the potential adverse outcomes of infection
in the individual cell is key to understanding the impact of viral
infection in complex tissue and indeed the whole host animal.
 Cellular tropism of viruses is determined by the presence of
appropriate cellular receptors and frequently, cell-type specific
transmission factor.
 Viruses typically encode genes that modulate host-cell function
for their own benefit and of course the host has elaborate
innate defense to restrict viral functions.
 Thus the viral and cellular factor that influence the outcome of
infection are often in delicate balance and easily shifted one
way or the other.

3. STAGES OF VIRAL INFECTION :-
 Primary infection occurs when virus enters the body through
different portals.
 The viruses then enter into the blood streams and targeted to
different organs, the stage is known as viremia.
 After entry into the predilected site they start their replication
and transmitted to different organ and may shed outside
through body secretions, the condition is referred as
secondary infection (infection of brain tissue by encephalitis
virus and liver by the hepatitis virus).

5. 1. Primary infection-
 Infection of cells in the general location where virus enters. Common for example
with cold viruses and Diarrhea causing viruses. Many viruses including HIV
initially infect cells in the infected area.
2. Viremia-
 Virus enters the blood system and can be detected in the blood stream. Not all
viruses do this. Some remain only localized.
3. Secondary infection-
 Infection of other organ of cell types by the virus. Many viruses have high affinity
for specific organs due to the presence of receptors or specific cell metabolic
functions.
 Examples are infection of salivary glands by mumps virus, brain tissue by
encephalitis virus, and liver tissue by hepatitis virus.

6.  Virus infection causes a wide variety of potentiality victorious changes in the many
different kinds of cells that occur in the animal host.
 The disruption of cellular function, the induction of cell death or transformation or
the activation of an inappropriate immune response are all potentiality manifested
as disease by the infected host.
 Although virus induced changes at the cellular, sub-cellular and molecular level are
most commonly studied in cultured cells, additional insight has been gained
through the use of organ culture, transcription of infected cells and tissues back
into experimental animals, and the experiment uses of genetically modified
laboratory animal in conjunction with molecular clo9nes of individual viruses.
 Many virus-cell interactions are transient and asynchronous, involving intermediate
steps on the pathway, each featuring dynamic interactions between different viral
and cellular components.

8. TYPES OF VIRUS-CELL INTERACTION
 Viral infection may be Cytocidal or non cytocydal and productive or non-
productive that is, not all infection leads to cell death or the production
and release of new versions.
 How-ever critical changes can occur in virus infected cells regardless of
whether the infection is productive or not.
 Some of the most important of all non productive virus cell interactions
are those associated with persistent infections or latent infections
 The term persistent infection simply describes an infection that lasts a
long time.
 The term latent infection describes an infection that "exists but is not
exhibited," i.e., an infection in which infectious virions is not formed.

10.  In either case, the virus or its genome is maintained indefinitely in the cell,
either by the integration of the viral nucleic acid into the host cell DNA or
by carriage of the viral nucleic acid in the form of an episome. In these
instances, the cell survives, indeed may divide repeatedly.
 In some instances such cells never release virions, in others the infection
may become productive when induced by an appropriate stimulus.
 Persistent or latent infections may also be associated with cell
transformation. The various types of interaction that can occur between
virus and cell are summarized

11. 1. CYTOCIDAL CHANGES IN VIRUS-INFECTED CELLS
 Cytopathic viruses kill the cells in which they replicate.
 When a monolayer of cultured cells is inoculated with a cytopathic virus, the first
round of infection yields progeny virus that spreads through the medium to infect
adjacent as well as distant cells in the culture may become infected.
 The resulting cell damage is known as a cytopathic effect (CPE).
 Cytopathic effect can usually be observed by low-power light microscopy of
unstained cell cultures.
 The nature of the cytopathic effect is often characteristic of the particular virus
involved and is therefore an important preliminary clue in the identification of
clinical isolates .
 Fixation and staining of infected cell monolayers may reveal further diagnostic
details.

12. Mechanisms of Cell Damage:-
1) Inhibition of Host Cell Nucleic Acid Synthesis
2) Inhibition of Host Cell RNA Transcription
3) Inhibition of Processing of Host Cell mRNAs
4) Inhibition of Host Cell Protein Synthesis
5) Cytopathic Effects of Toxic Viral Proteins
6) Cytopathic Changes Involving Cell Membranes
7) Cell Membrane Fusion and Syncytium Formation (cell fusion)

13. Mechanisms of Cell Damage

14. 2. NON-CYTOCIDAL CHANGES IN VIRUS-INFECTED CELLS:-
 Non-Cytocidal viruses usually don’t kill cell in which they will replicate.
 They cause persistent infection, in which infected cell produce and release virions
but overall cellular metabolism is little affected.
 In many instances the infected cells even continue grow and divided.
 This type of virus-cell interaction is found in cells infected in several RNA viruses
by
A. Effect of Non-Cytocidal Viral Infection on Function of Specialized Cell
B. Inclusion Bodies (virus specific intracellular globular masses produced in host
during replication)
C. Polarity of Viral Infection
D. Ultrastructural Changes in Virus-Infected Cells

15. Immunological outcomes of heterologous viral
infections.

16. PATHOGENEIS OF VIRAL INFECTIONS:-
Viral Entry
Three requirements must be satisfied to ensure successful infection in
an individual host:
• Sufficient virus must be available to initiate infection
• Cells at the site of infection must be accessible, susceptible, and
permissive for the virus
• Local host anti-viral defense systems must be absent or initially
ineffective.
To infect its host, a virus must first enter cells at a body surface.
Common sites of entry include the mucosal linings of the
Respiratory tract, alimentary tract , and urogenital tracts, skin,
congenital, Conjunctiva.

18. Respiratory Tract
 The most common route of viral entry is through the respiratory tract.
 The combined absorptive area of the human lung is almost 140 m2.
 Humans have a resting ventilation rate of 6 liters of air per minute, which introduces
large numbers of foreign particles and aerosolized droplets into the lungs with every
breath.
 Viruses enter the host through droplets expelled from the nose or mouth of infected
persons during talking, coughing or sneezing.
 Viruses may enter the respiratory tract in the form of aerosolized droplets expelled by
an infected individual by coughing or sneezing, or through contact with saliva from
an infected individual.
 Larger virus-containing droplets are deposited in the nose, while smaller droplets find
their way into the airways or the alveoli.
 To infect the respiratory tract successfully, viruses must not be swept away by
mucus, neutralized by antibody, or destroyed by alveolar macrophages.

20. Urogenital Tract
 Some viruses enter the urogenital tract as a result of sexual activities.
 The urogenital tract is well protected by physical barriers, including mucus and low pH (in the
case of the vagina).
 Normal sexual activity can result in minute tears or abrasions in the vaginal epithelium or the
urethra, allowing viruses to enter.
 Some viruses infect the epithelium and produce local lesions (e.g., certain human
papillomaviruses, which cause genital warts).
 Other viruses gain access to cells in the underlying tissues and infect cells of the immune
system (e.g., human immunodeficiency virus type 1), or sensory and autonomic neurons (in
the case of herpes simplex viruses).

21. Eyes
 The epithelium covering the exposed part of the sclera and the conjunctivae is the
route of entry for several viruses.
 Every few seconds the eyelid passes over the sclera, bathing it in secretions that
wash away foreign particles.
 There is usually little opportunity for viral infection of the eye, unless it is injured by
abrasion. Direct inoculation into the eye may occur during ophthalmologic
procedures or from environmental contamination (e.g., improperly sanitized
swimming pools).
 In most cases, replication is localized and results in inflammation of the conjunctiva
(conjunctivitis). Systemic spread of the virus from the eye is rare, although it does
occur (e.g., paralytic illness after enterovirus 70 conjunctivitis).
 Herpesviruses can also infect the cornea at the site of a scratch or other injury. This
infection may lead to immune destruction of the cornea and blindness.

22. Skin
 The skin of most animals is an effective barrier against viral infections, as the dead
outer layer cannot support viral growth.
 Entry through this organ occurs primarily when its integrity is breached by breaks or
punctures.
 Replication is usually limited to the site of entry because the epidermis is devoid of
blood or lymphatic vessels that could provide pathways for further spread.
 Other viruses can gain entry to the vascularized dermis through the bites of
arthropod vectors such as mosquitoes, mites, ticks, and sandflies.
 Even deeper inoculation, into the tissue and muscle below the dermis, can occur by
hypodermic needle punctures, body piercing or tattooing, animal bites, or sexual
contact when body fluids are mingled through skin abrasions or ulcerations.

23. Routes of virus entry into the host

24. Alimentary Tract
 The alimentary tract is a common route of infection and dispersal.
 Eating, drinking, and some social activities routinely place viruses in the alimentary
tract.
 It is designed to mix, digest, and absorb food, providing a good opportunity for
viruses to encounter a susceptible cell and to interact with cells of the circulatory,
lymphatic, and immune systems.
 It is an extremely hostile environment for a virus.
 The stomach is acidic, the intestine is alkaline, digestive enzymes and bile
detergents abound, mucus lines the epithelium, and the lumen surfaces of intestines
contain antibodies and phagocytic cells
 The hostile environment of the alimentary tract actually facilitates infection by some
viruses. For example, reovirus particles are converted by host proteases in the
intestinal lumen into infectious subviral particles, the forms that subsequently infect
intestinal cells

25. Viral Spread
 Following replication at the site of entry, virus particles can remain localized, or can
spread to other tissues .
 Local spread of the infection in the epithelium occurs when newly released virus
infects adjacent cells.
 These infections are usually contained by the physical constraints of the tissue and
brought under control by the intrinsic and immune defences.
 An infection that spreads beyond the primary site of infection is called
disseminated.
 If many organs become infected, the infection is described as systemic.

26.  For an infection to spread beyond the primary site, physical and immune barriers
must be breached.
 After crossing the epithelium, virus particles reach the basement membrane .
 The integrity of that structure may be compromised by epithelial cell destruction and
inflammation.
 Below the basement membrane are sub-epithelial tissues, where the virus
encounters tissue fluids, the lymphatic system, and phagocytes.
 All three play significant roles in clearing foreign particles, but also may disseminate
infectious virus from the primary site of infection.
View of the intestinal wall, showing a typical M cell surrounded by
enterocytes

27. Hematogenous Spread
 Viruses that escape from local defenses to produce a disseminated infection often
do so by entering the bloodstream (hematogenous spread). Virus particles may
enter the blood directly through capillaries, by replicating in endothelial cells, or
through inoculation by a vector bite.
 viremia = presence of infectious virus particles in the blood. T
 hese virions may be free in the blood or contained within infected cells such as
lymphocytes Active viremia is produced by virus replication, while passive
viremia results when virus particles are introduced into the blood without viral
replication at the site of entry (injection of a virus suspension into a vein).
 Progeny virions released into the blood after initial replication at the site of entry
constitute primary viremia.
 secondary viremia =Delayed appearance of a high concentration of infectious
virus in the blood is termed secondary viremia.

28. Neural Spread
 Many viruses spread from the primary site of infection by entering local
nerve ending.
 For certain viruses (e.g., rabies virus and alpha herpesviruses), neuronal
spread is the definitive characteristic of their pathogenesis.

29. Organ Invasion
 Once virions enter the blood and are dispersed from the
primary site, any subsequent replication requires invasion of
new cells and tissues.
 Three main types of blood vessel-tissue junctions provide
routes of tissue invasion

30. The Liver, Spleen, Bone Marrow, and Adrenal Glands
 These tissues are characterized by the presence of sinusoids lined with macrophages. Such
macrophages, known as the reticuloendothelial system, function to filter the blood and remove
foreign particles.
 They often provide a portal of entry into various tissues.
 For example, viruses that infect the liver usually enter from the blood. The presence of virus
particles in the blood invariably leads to the infection of Kupffer cells, the macrophages that line
the liver sinusoids
NOTE:- Tropism
Most viruses do not infect all the cells of a host but are restricted to specific cell types of certain
organs. The spectrum of tissues infected by a virus is called tropism.
For example, an enterotropic virus replicates in the gut, whereas a neurotropic virus replicates in
cells of the nervous system. Some viruses are pantropic, infecting and replicating in many cell types
and tissues.

31. HOST RESPONSE TO VIRUS INFECTION:-
 The out come of virus infection depends on the virulence of the infecting
strain and resistance offered by the host
 The mechnism of the host resistance my be of following types :-
1. NON-SPECIFICE RESPONSES (NON-IMMUNOLOGICAL)
A. Age
B. Hormones
C. Malnutrition
D. Body Temperature
E. Phagocytosis
F. Inferferons (ALFA,BETA,GAMMA)
2.IMMUNOLOGICAL RESPONSES
A. Abtibody-Mediated Immunity
B. Cell-Mediated Immunity (CMI)

32. 1. NON-SPECIFIC RESPONSES:-
A. AGE:-
 Most of the viral infections tend to be most serious of extrems of life.
 Rotaviruses case severe disese only in infants.
B. HORMONES:-
 Corticostriods administration enhances most viral infections.
 Without judgment the use of steriods in the treatment of
herpetoconjunctivitis may casues blindnes.
C. MALNUTRITION:-
 It interferes with the humoral and cell-mediated immune responses therefore
it can increase viral infection.

33. D.BODY TEMPERATURE:-
 Most of the viral infections are accompained by fever.
 Fever may act as a natural defence mechanism against viral infections as most viruses are inhibited by
temperaturea above 39 Deg.c.
E.PHAGOCYTOSIS:-
 Macrphages phagocytose viruses and are important in clearing viruses from blood-stream.
 Polymorphonuclear leucocyte don not play any significant role.
F. INTERFERONS:-
 IFNs are family of glycoproteins produced by cells on induction by viral or non-viral microbs.
 These have antiviral activity by inhabiting protein synthesis.
TYPES:-
i. IFN-ALFA:- Produced by leucocytes having antiviral activity.
ii. IFN-BETA:-Produced by fibroblasts and epithelial cells having antiviral activity.
iii. IFN-GAMMA:- Produced by T-Lymphocytes and NK cells having immunoregulatory
functions.
Alfa and beta produced three enzymes (synthetase,Rnase L and Protein Kinase) and inhibit protein synthesis.

34. IMMUNOLOGICAL RESPONES TO VIRAL INFECTION:-
Viruses in general are good antigens and induce both the
ANTIBODY-MEDIATED IMMUITY CELL-MEDIATED IMMUNITY

35. A. ANTIBODY-MEDIATED IMMUITY
 IgG & IgM play a important role in blood and tissues while IgA is more important in mucosal
surfaces.
 All three antibodies may act in the following ways:-
i. Neutralisation of virus which prevents attachment, penetration or subsequent events.
ii. Lysis by complement or destruction by phagoctes or killer (K) lymphocytes.
iii. Immune opsonisation of virus for phagocytosis and destruction of virus by macrophages.
B. CELL-MEDIATED IMMUNITY (CMI)
 CMI prevents infection of target organs and promotes recovery from diseases by destroying
virus and virus-infected cells.
 Mechanisms involved are
i. Cytolysis by cytotoxic T-Cels and NK Cells
ii. Antibody-Dependent cell mediated cytotoxicity
iii. Antibody- Complement-mediated cytotoxicity.

36. CONCLUSION
 The non-specific host defences function early in the encounter
with virus to prevent or limit infection while the specific host
defences function after infection in recovery immunity to
subsequent challenges.
 Although the host defence mechanisms involved in a particular
viral infection will vary depending on the virus, dose and portal
of entry.

37. THANK YOU