PATHOGENIC EFFECTS OF

VIRUSES
Defn:
 Obligate intracellular microparasites,
size 20-300 nm.
 Depend on host metabolism for their
replication.
 After invading cells, they divert the
metabolic function of the cells for
synthesis of viral nucleic acids and
proteins
Classification:
 Based on nucleic acid content of the
core either DNA or RNA.
 Shape of the protein coat or capsid-
Spherical or cylindrical
Barrier to most viruses.
 Skin penetrated by biting arthropods
introducing the virus eg yellow fever.
 Needles- HBV, HIV or blood transfusion.
 Animal bites- rabies.
 Respiratory, G.I.T, GUT etc.
Steps in viral replication.
 Attachment of the virus to host cell membrane.
 Viral penetration of host cell membrane.
 Uncoating of the virus particle ie protein
capsid.
 Synthesis of viral nucleic acid and protein.
 Assembly of structurally mature viruses.
 Release of viruses from host cell.
Infection at cellular level.
Extracellular viral particles (virions) occur
in different forms:
1. Simple virions- contain only the viral
genome either DNA or RNA, not both.
 Usually with coat or capsid proteins to
form nucleocapsid.
2. Complex viruses- may have double
capsid shell, or the nucleocapsid
surrounded by an envelope ( glycolipid
or glycoprotein).
 Extracellular virions are incapable of
independent replication.
 When introduced into susceptible cells
replication can take place.
Viral genome must pass through 2
barriers:
i. protective layer of virus ( capsid or
envelope)
ii. plasma membrane of the host cell
Initial step:
 Attachment of virion to surface of host
cell
“SPECIFIC RECEPTORS”
 Absence or presence of these surface
receptors determines the HOST
range and tissue tropism for animal
viruses.
 For many ENVELOPED viruses viral
attachment protein is a glycoprotein.
 For nonenveloped viruses, it is one of
the capsid protein.
 Host cell receptors for most virus
attachment not all known!
 HIV (retrovirus)- Primary receptor CD4
Ag on T helper lymphocytes
 Poliovirus – CD 155 receptors present
on cells in human gastrointestinal tract.
 Several enveloped viruses eg myxoviruses –
bind to determinants containing sialic acid
residues at the sugar chains of
glycoproteins/lipids.
 EBV – binds to the complement receptor on
macrophages (CD 21).
 Rabies virus – binds to acetyl choline receptor
on neurons.
 Rhinoviruses bind to the adhesion protein
ICAM-1 on mucosal cells.
Viral entry mechanisms:
Entire virion or a portion containing genome
enters into cell cytoplasm by one of 3 ways:
1. Translocation of entire virus across plasma
membrane,
2. Fusion of viral envelope with cell membrane
, OR
3. Receptor mediated endocytosis (REM) of
the virus and fusion with endosomes.
Eclipse phase:
 After nucleic acid release, it becomes
unidentifiable for a few hours.
 The nucleic acid during this phase is not
infectious.
Invasion of cells.
 After invasion of cells – the virus diverts the
biosynthetic and metabolic functions of host
cell for synthesis of viral coded nucleic
acids and proteins.
 Separates its genome from capsid,
 Replicates using enzymes-
a. RNA polymerase,from -ve stranded RNA
viruses into +ve-stranded mRNA
b. Reverse transcriptase- retroviruses to
generate DNA from RNA template.
 Viruses also use host enzymes for viral
synthesis, which may be present in some
tissue and not in others.
 Newly synthesized viral genomes and
capsid proteins assembled into progeny
virions.
 Released directly (uncapsulated viruses)
or by budding(encapsulated viruses).
 Infection may be abortive – if incomplete
viral replication.
 Latent- eg in Herpes zoster virus
 Persistent eg in HBV where virion
synthesis is continuous.
Viral latency: Certain viruses esp Herpes
group can remain dormant within host
cell for years.
 They remain integrated within the cell
genome until triggered by a variety of
stimuli to undergo replication.
Cell to cell spread.
 After a complete cycle of replication,
virus is released either by cell lysis or by
budding to infect other cells.
 Extracellular virions however, may
encounter antiviral antibodies and
cellular defence mechanisms
 Some viruses such as paramyxoviridae
are able to bring about fusion of plasma
membranes of adjacent cells, and so the
virus passes freely from one cell to the
other.
Effects of viral replication on host cell
morphology:
 Vary from little or none to total
dessolution of cells.
 Some of the changes seen in cytological
or histological preparations.
 They may be typical or highly suggestive
of causative agent.
 eg presence of inclusion bodies and
formation of giant cells in infected cells.
 Inclusion bodies ( intranuclear or
intracytoplasmic) represent masses of
viral particles or remnants of viral
replication.
CMV
Rabies inclusions
Measles giant cells
Host Response to viral infections:
The main pathologic and immunologic
response are;
 Inflammation
 Antibody formation
 Interferon formation
 Cellular immunity
 Inflammation- already covered in lecture-
predominant cell is lymphocyte.
 Antibody formation- include Ig M, Ig G
and Ig A.
 Ig M detected early in disease- evidence
of infection
 Interferon production, important for
termination of infection.
 Are glycoproteins produced by
macrophages in response to viral infection.
 Their production may also be stimulated by
other microbial agents, endotoxins and
inducer substances.
 When taken by other cells , it makes them
refractory to virus infection
Classified into:
 Alpha interferon and beta interferon
produced by macrophages.
 Gamma IFN produced by activated T
lymphocytes
Cell immunity:
 Plays an important part.
 Responsible cell- T lymphocyte.
 2 main functions:
 Cytotoxic effects- destroys virus infected
cells
 Recruitment of macrophages- important
for phagocytosis of viral particles.
Viruses kill cells by :
 Inhibition of host cell DNA , RNA, or
protein synthesis
 Direct membrane damage.
 Viral replication lyses the host cell .
 Viral proteins on surface recognized by
the immune system.
 Cell transformation leading to tumours.
end