1. The document discusses virus-host interactions at the cellular, individual, and community levels and the various effects viruses can have on cells, including no effect, proliferation, malignant transformation, and cell death. 2. It describes how viruses like poliovirus cause cell death or lysis, while others cause proliferation or malignant transformation. Cellular injury may be caused by viral proteins, accumulation of viral molecules, altered membranes and chromosomes, fusion of adjacent cells, inclusion bodies, and viral antigens on the cell surface. 3. The host response involves non-specific responses like fever and interferons as well as immune responses through antibodies and cell-mediated immunity which work to neutralize viruses, opsonize them for destruction

1. By – Dr.D.W.Deshkar
Department of Microbiology

2. VIRUS – HOST INTERACTIONS
 Cellular level
 Individual level
 Community level
@ Cellular level – may cause broad spectrum of
effects -
No effect Cellular
proliferation
Malignant
transformation
Cell death
Host response is the
outcome of the
complex interplay
between host and virus.

3. VIRUS – HOST INTERACTIONS
Some viruses, like Poliovirus – cause cell death
( ) or even lysis ( ).
Other viruses may cause cellular proliferation
( molluscum contagiosum ) or malignant transformation
( ).

4. CELLULAR INJURY MAY BE DUE TO
A NUMBER OF CAUSES
1.Early or nonstructural viral proteins often cause a shut-down
of host protein and DNA synthesis.
2.Large amounts of viral macromolecules that accumulate in
the infected cell may distort the cellular architecture and exert
a toxic effect.
3.The permeability of plasma membranes may be altered

5. CELLULAR INJURY MAY BE DUE TO
A NUMBER OF CAUSES
4.Many viruses produce alterations in the cytoplasmic membrane
of infected cells.
5.Certain viruses cause damage to the chromosomes of host cells
(eg: measles, mumps, adenovirus, Varicella, cytomegaloviruses).
6. Some ( such as respiratory syncytial virus) cause fusion of adjacent
cell membrane leading to polykaryocytosis or Syncytium
formation.

6. CELLULAR INJURY MAY BE DUE TO
A NUMBER OF CAUSES
7. Virus coded antigens may appear on the surface of infected cells.
These antigens may confer new properties on the cells.
• E.g. – viral haemagglutinin appears on the surface of cells
infected with the influenza virus and causes adsorption of
erythrocytes to the cell surface ( haemadsorption).
• Virus coded antigens also appear on the surface of cells
transformed by oncogenic viruses.
8. Inclusion bodies.

7. INCLUSION BODIES
 Most characteristic histological feature in virus infected cells is
the appearance of inclusion bodies.
 Structures with distinct size, shape , location and staining
properties
 Can be seen under light microscope after staining
 May be seen in cytoplasm or nucleus
 Generally acidophilic in nature –Pink in colour on staining with
Giemsa or Eosin methylene blue stains
 Some may be basophilic as well

8. INCLUSION BODIES
 Help in diagnosis
–Negribodies –intra cytoplasmic inclusion –Rabies
–Guarnieribodies –Vaccinia
–Bollinger bodies –fowl pox
–Molluscum bodies –molluscum contagiosum
–Cowdry type A –Herpes virus , Yellow fever virus
–Cowdry type B –Adenovirus, Polio virus
 Inclusion bodies my be an aggregate of virions or collection of
viral antigens or the degenerative changes produced by viral
infection.

9. NEGRIBODIES –RABIES –
INTRACYTOPLASMIC

10. GUARNIERIBODIES –VACCINIA

11. BOLLINGER BODIES –FOWL POX

12. MOLLUSCUM BODIES –
MOLLUSCUM CONTAGIOSUM

13. COWDRY TYPE A

14. COWDRY TYPE B

15. PATHOGENESIS OF VIRAL
INFECTIONS
• Depending on the clinical outcome, viral infections can be
classified as
1. Inapparent (subclinical)
2. Apparent (clinical or overt)
a) acute b) subacute c) chronic
• Latent infections
 Herpes simplex and Varicella-zoster viruses remain latent in
nerve root ganglia, to be reactivated periodically
 HBV and HIV infections
 Slow viral diseases

16. VIRUSES ENTER THE BODY THROUGH
THE FOLLOWING ROUTES
• 1. Respiratory tract
• 2. Alimentary tract
• 3. Skin
• 4. Genital tract
• 5. Conjunctiva
• 6. Congenital

17. ROUTES OF TRANSMISSION OF VIRAL
INFECTIONS
Route of
transmission
Viruses
Respiratory tract Influenza, Parainfluenza, RSV, Measles, Mumps, Rubella,
Rhinovirus, Adenovirus Coronavirus, Varicella-zoster, CMV,
EBV
Alimentary tract Poliovirus, Adenovirus, Hepatitis A, E viruses, Rotavirus,
Norwalk virus
Skin Herpes simplex, Papilloma viruses Molluscum contagiosum,
Rabies virus Arboviruses, HBV, HCV, HIV, HTLV
Genital tract Herpes simplex viruses, HBV, HCV HIV, Papillomaviruses
Conjunctiva Some adenoviruses, Few enteroviruses

18. CONGENITAL INFECTION
• Many viruses are transmitted vertically from parent to progeny
• Congenital infection may occur at any stage from the
development of the ovum up to birth
• In acute systemic infections, congenital infection usually leads
to fetal death and abortion
• Rubella and cytomegalovirus produce maldevelopment or
severe neonatal disease
• HIV, HSV, many tumor viruses cause congenital infection

19. ROUTE OF ENTRY
 Respiratory tract (Most common)
• Multiply locally Blood/Lymph Extensive multiplication
Disease.
• Small pox, chicken pox
• Influenza , Rhinovirus (stay in respiratory tract itself)
 Alimentary tract
• All enveloped viruses are destroyed by bile
• Rhinovirus is inactivated by gastric juice
• Enterovirus, adenovirus, reo virus, hepatitis virus
• Some multiply in GIT and transported to target organs (eg.Poliovirus)
 Genital tract
Conjunctiva
Skin
Vertical transmission –Mother to baby

20. • Skin
–Produce few local lesions
–Papilloma, Vaccinia, cowpox & molluscum contagiosum.
–Viruses can enter through break in skin
–Abrasions –Papillomaviruses
–Insect bites –Arboviruses
–Animal bites –Rabies
–Injections –Hepatitis
•Genital tract
–Human immuno deficiency virus
ROUTE OF ENTRY

21. ROUTE OF ENTRY
• Conjunctiva
–Local disease –Adenovirus
–Systemic disease –Measles
•Vertical transmission –Mother to baby
–May occur at any stage till birth
–Usually leads to fetal death and abortion
–Maldevelopment–Rubella and Cytomegalovirus
–Many tumor virus spread via this route

22. SPREAD OF VIRUS IN THE BODY

23. SPREAD OF VIRUS IN THE BODY

24. SCHEMATIC ILLUSTRATION OF PATHOGENESIS
OF MOUSE POX & POLIO VIRUS

25. PATHOGENESIS

26. INCUBATION period
• It is the time taken for the virus to spread from the site of
entry to the target organs for the production of lesions.
• Its duration is therefore influenced by the relation between
the site of entry, multiplication and lesion.
• The incubation period in HBV may be 2-6 months and in slow
viral infections, many years.
• Papilloma and molluscum contagiosum have long incubation
periods, probably because the viruses multiply slowly

27. HOST RESPONSE TO VIRUS
INFECTIONS
1.Non-Specific responses
2. Immunological
responses
a) Humoral immunity
(AMI)
b) Cell-mediated
immunity (CMI)

28. NON-SPECIFIC RESPONSES
• 1.Age
Most of the viral infections
tend to be more serious at
extremes of life
Rotaviruses cause severe
disease only in infants

29. 2. Hormones
Corticosteroids administration enhances most viral infections
• The particularly severe course of many viral infections in pregnancy
may be related to the hormonal changes
3. Malnutrition
• Malnutrition interferes with the humoral and cell-mediated immune
responses, therefore it can exacerbate viral infections (eg: measles –
higher incidence of complications and a higher case fatality rate in
malnourished children)
4. Body temperature
• Fever may act as a natural defense mechanism against viral infections
as most viruses are inhibited by temperatures above 390C
NON-SPECIFIC RESPONSES

30. NON-SPECIFIC RESPONSES
5. Phagocytosis
 Macrophages phagocytose viruses and are important in clearing
viruses from blood stream
 Polymorphonuclear leucocytes do not play any significant role
6. Interferons
 Interferons are a family of glycoproteins produced by cells on
induction by viral or nonviral inducers
 Interferon by itself has no direct action on viruses but acts on other
cells of the same species, rendering them refractory to viral
infection
 On exposure to interferon, cells produce a protein (translation
inhibiting protein, TIP) which selectively inhibits translation of
viral mRNA

31. TYPES OF INTERFERONS
 They are classified into three types
1. IFN-α
 It is induced by virus infection and produced by leucocytes
 It has antiviral activity
2. IFN-β
 It is also induced by virus infection but produced by
fibroblasts and epithelial cells
 It also has antiviral activity

32. TYPES OF INTERFERONS
3. IFN-γ
 Produced by T-lymphocytes and NK cells, on stimulation by antigens
or mitogens
 It is a lymphokine with Immunoregulatory functions
 It enhances MHC antigens and activates cytotoxic T-lymphocytes,
macrophages and NK cells
 Modulates antibody formation and suppresses DTH
Mechanism of action
 IFN-α and IFN-β induce the production of three enzymes namely
protein kinase, an Oligonucleotide synthetase and an Rnase. This
leads to inhibition of viral protein synthesis but does not affect host
protein synthesis

33. BIOLOGICAL EFFECTS OF INTERFERON
• Anti-Viral : resistance to infection
• Anti –Microbial: Resistance to intracellular infections (Toxoplasma,
Chlamydia, Malaria)
• Cellular effects : Inhibition of cell growth and proliferation,
Increased expression of MHC antigens on cell surface
• Immunoregulatory:
–Increases activity of Natural killer (NK) calls and T cells.
–Activates cell destruction activity of macrophage
–Moderates antibody formation
–Activates suppressor T cells
–Suppresses DTH

34. IMMUNOLOGICAL RESPONSES
1. Antibody-mediated immunity
 IgG, IgM, IgA antibodies are produced in response to virus
infection
 IgG and IgM play a major role in blood and tissue spaces
while IgA is more important in mucosal surfaces
 IgA is important in resistance to infection of the respiratory,
intestinal and urogenital tracts

35. ANTIBODIES MAY ACT IN THE
FOLLOWING WAYS
• Neutralization of virus which prevents attachment, penetration
or subsequent events
• Antibody may attach to viral antigens on the surface of infected
cells, rendering these cells prone to lysis by complement or
destruction by phagocytes or killer lymphocytes
• Immune opsonisation of virus for phagocytosis and destruction
of virus by macrophages

36. CELL-MEDIATED IMMUNITY (CMI)
• CMI prevents infection of target organs and promotes
recovery from disease by destroying virus and virus-infected
cells. The different mechanisms involved for virus destruction
are as follows
• 1. Cytolysis by cytotoxic T-cells and Natural-killer (NK) cells
• 2. Antibody-dependent cell-mediated cytotoxicity (ADCC)
• 3. Antibody-complement-mediated cytotoxicity

37. IMMUNOPROPHYLAXIS
1. Active immunization
2. Passive immunization
• Active immunization
• Viral vaccines
• a) Live viral vaccines
• b) Killed viral vaccines

38. LIVE VIRAL VACCINES
 They are prepared from
• Attenuated strain (eg: yellow fever vaccines)
• Temperature sensitive (ts) mutants (eg: influenza)
• Live recombinant viruses (eg: influenza)
Advantages -
1. A single dose of live vaccine is usually sufficient
2. They may be administered by the route of natural infection so
that local immunity is induced

39. LIVE VIRAL VACCINES
Advantages –
3. They induce a wide spectrum of immunoglobulins against the
whole range of viral antigens
4. They also induce cell mediated immunity
5. They can in general be prepared more economically, and
administered more conveniently for mass immunization

40. LIVE VIRAL VACCINES
Disadvantages –
1. There is a risk, however remote, of reversion of virulence
2. The vaccine may be contaminated with potentially dangerous
viruses (eg: oncogenic viruses)
3. Live viral vaccines are heat-labile and they have to be kept
under strict refrigeration

41. LIVE VIRAL VACCINES
Disadvantages –
1. There is a risk, however remote, of reversion of virulence
2. The vaccine may be contaminated with potentially dangerous
viruses (eg: oncogenic viruses)
3. Live viral vaccines are heat-labile and they have to be kept
under strict refrigeration
4. Interference by preexisting viruses
5. The virus may spread from the vaccines to contact
6. Some live viral vaccines may cause local but remote
complications

42. KILLED VIRAL VACCINES
• Killed vaccines are prepared by inactivating viruses with heat,
phenol, beta- propiolactone and formaldehyde
• Advantages
• 1. Safety and stability
• 2. They can be given in combination as polyvalent vaccines
• 3. There is no danger of spread of virus from the vaccinee
• Disadvantages
1. Multiple injections are needed
2. These vaccines have to be given by injection, therefore,
local immunity (IgA immunoglobulins) immunity fails to develop
3. Cell mediated immunity is not induced

43. PASSIVE IMMUNISATION
• Passive immunization with human gamma globulin,
convalescent serum or specific immune globulin gives
temporary protection against many viral diseases (eg:
measles, mumps and infectious hepatitis)
• Indicated only when non immune individuals who are at
special risk are exposed to infection
• Combined active and passive immunization is an established
method for the prevention of rabies

44. TYPES OF VACCINES

45. CHEMOPROPHYLAXIS AND
CHEMOTHERAPY OF VIRAL DISEASES
Mode of action Antiviral agents Active against
Inhibits viral DNA
polymerase
a) Acyclovir
b) Ganciclovir
c) Ribavirin
a) Herpes simplex, VZV
b) Cytomegalovirus
c) RSV, Lassa virus
Inhibits reverse
transcriptase
a) Zidovudine
b) Dideoxycytidine
c) Dideoxyinosine
HIV
Inhibits proteases a) Indinavir
b) Nelfinavir
c) Ritonavir
d) Saquinavir
HIV
Blocks penetration of
virus
into cells
Blocks penetration of virus
into cells
Amantadine
Influenza virus
Inhibits protein
synthesis
Interferons Many viruses