talks about virus

1. VIRAL PATHOGENICITY
DR. UBONG UDOH
CLINICAL MICROBIOLOGIST
FACULTY OF BASIC MEDICAL SCIENCES

2. Introduction
• In order for an infection to occur, a virus must first
replicate in a host.
• Viral disease occurs as a result of the interaction
between the virus and host factors.
• Clinical disease occurs when a viral infection results
in signs and symptoms, however most viral
infections do not produce symptoms and are
described as subclinical (inapparent) disease.
• The same virus may produce a variety of diseases
while the same disease may be produced by a
variety of viruses.

3. Steps in viral pathogenesis
• Entry of virus into the host.
• Primary replication.
• Viral spread.
• Host defense response.
• Shedding and transmission of infection.
*it must first be virent
measles is respiratory
virus likes macrophage

4. Viral entry into host
• Virus attaches to cells at one of the body surfaces
(the skin, respiratory tract, gastrointestinal tract,
urogenital tract or conjunctiva) and then enters.
• Viruses may enter through virus contaminated
-needles
-therapeutic substances
-blood or blood products
• Also bites from insect vectors or sick animal (e.g.
rabies) introduces virus into the host.

5. Replication
• Viruses usually initiate infection by replicating at
the portal of entry.
• Respiratory viruses replicate in;
 epithelial cells lining the alveoli or respiratory
tract
 phagocytic cells located either in the respiratory
or sub epithelial spaces.
• Some others replicate in the skin to produce
local lesions e.g. Poxviruses, Papillomavirus

6. Steps in viral replication
• Attachment: the virus attaches to the host cell
using specialized attachment sites distributed over
the surface of the virion to specific cellular
receptors.
• Penetration: commonly occurs by receptor
mediated endocytosis and the virion contained
within a cytoplasmic vacuole.
• Uncoating: rearrangement of coat components,
causing the extrusion of the viral core into host
cell cytosol.

7. Steps in viral replication
• Genome synthesis: virulent viruses shut off
cellular protein synthesis and disaggregate cellular
polyribosomes favouring a shift to viral synthesis
using varied mechanisms.
• Assembly: some viruses (herpesviruses) assemble
in the nucleus while others assemble in the
cytoplasm. Chaperones are involved.
• Maturation: this proceeds differently for naked,
enveloped and complex viruses.

8. Replication Cycle

9. Viral spread
• Lymphatic: the first step in the dissemination of
infection is the transport of virus via efferent
lymphatic drainage from the primary site of
infection to regional lymph nodes.
• Neural: some viruses can spread along peripheral
nerves. Through this route, Rabies virus reaches
the brain to cause disease, and Herpes simplex
virus reaches the ganglia to initiate latent
infections.

10. Viral spread
• Blood:
 Active viraemia;
 Primary viraemia: viruses from regional lymph nodes enter
the bloodstream and are disseminated to the muscles, bone
marrow, liver, spleen and blood vessels, where further
replication takes place.
 Secondary viraemia: from the RES the viruses again enter
the blood stream to reach their target organs. The viruses
again replicate in these organs.
 Passive viraemia; following direct inoculation e.g.
arthropod vectors, blood transfusion or I.V. drug abuse.

11. Host response to viral infection
• Immunological
Humoral (antibody-mediated) immunity- the
production of immunoglobulins IgM, IgA and IgG play
an important role in immunity to virus infection. They
can directly affect virus infectivity by neutralizing the
processes of attachment, entry and uncoating.
Cell-mediated immunity-protects against those viral
infections which are not associated with viraemia, but
where the virus spreads from cell-to-cell by fusion
with antigenic alterations to cell membranes e.g.
Herpes or Paramyxoviruses.

12. Host response to viral infection
• Immunological
• Macrophages; recognize virus-infected cells and
kill them (cytotoxic activity). They also kill cells
coated with IgG antibodies by ADCC.
• Lymphocytes (T-cells);
 Cytotoxic T-cells are generated in response to
viral antigens on infected cells and kill the cells
thereby preventing the spread of infection.

13. Host response to viral infection
Helper T-cells are involved in generation of
cytotoxic T-cells and in assisting B-cells to make
antibody. In addition, lymphokines secreted by
T-cells can recruit and activate macrophages and
NK cells (which directly kill virally infected cells).

14. Host response to viral infection
• Non-immunological: these are the early non-
specific responses put up by the host and include
general physiological defenses;
– Inflammation
– Phagocytosis
– NK cells
– Interferon
– Complement
– Pyrexia
– Cytokines

15. Shedding & transmission of infection
• This is the last step in viral pathogenesis and is
imperative for the maintenance of a viral infection in a
host population.
• Most shedding usually occurs from the body surface
utilized for the entry of viruses into the host.
• Shedding occurs into respiratory aerosols, faeces, urine,
blood, genital fluid and milk.
• It is transmitted vertically (transplacentally) or
horizontally to susceptible host. Shedding does not
occur in infection of the brain. This is referred to as a
dead-end infection.

16. Oncogenicity
• The ability to induce malignant transformation
of host cells.
• Peyton Rous first demonstrated that viral
infections can cause cancer.
Oncogenic viruses cause cancer by altering normal
cell growth through;
Increasing saturation density
Negating growth factor requirements
Negating anchorage dependence

17. Viruses & associated malignancies
• HPV- cervical cancer & anogenital neoplasms.
• EBV- Burkitt’s lymphoma, Hodgkin’s disease, B-cell
lymphoma & nasopharyngeal carcinoma.
• Human herpesvirus 8- Kaposi sarcoma & primary
effusion lymphoma in persons with HIV infection
• HBV and HCV- hepatocellular carcinoma.
• HTLV- Adult T-cell leukaemia.
• HIV- AIDS related malignancies.

18. General oncogenic mechanisms
• Persistence of infection.
• Host immune response.
• Viral oncogenic virulence.
• Cell susceptibility to viral infection &
transformation.
• Retention of viral nucleic acid in host cell.

19. Conclusion