INFECTION AND DISEASE

LECTURE 4

Viruses part I
What are Viruses ?
 Viruses
Obligate intracellular
parasites

Nucleic acid genome: DNA

or RNA

Protein coat: Protection,

entry (capsid)

Envelope (some viruses):

host / viral;
lipids/glycoproteins; entry

Size: 20-350nm

3
Size of viruses
Viruses cannot be seen using a light
microscope
 How are viruses
different from bacteria ?
 Viruses

DNA / RNA in a protein coat

Do not have protein synthesis

apparatus

Require host cells to replicate

Smaller in size
 Are viruses living things ?
Do not breathe

Do not move

Able to replicate

? Living things
 Classification of viruses
No taxa above Family
(no order, class,
phylum, kingdom etc)

Genus / species name

ends in virus

- binomial nomenclature
is not yet adopted for
viruses
 Example
Genus Varicella zoster virus
Common name chickenpox virus
Disease chickenpox
Baltimore classification
Viral Proteins
 Viral proteins
Structural protect viral
genome and help in
attachment. Eg. Capsid

Non-structural essential
for initiation of replicative
cycle. Eg. reverse
trasncriptase, Proteases

Virus envelope contains

glycoproteins and lipids
Virus envelope
 Virus envelope
Contain lipids and glycoproteins

Lipids cellular membranes derived (through

budding)

Glycoprotein- virus encoded

Role in attachment to host cell

Loss of envelope = loss of infectivity

Envelope
Viral nucleic acids
 Virus nucleic acids

DNA genomes- 3 Kb to 375 Kb

RNA genomes 7Kb to 30 Kb

Viral nucleic acids linear , circular,

segmented (RNA only).
 Nucleocapsid

Nucleic acid + protein coat

Structural unit of the protein

coat (capsid) is the capsomer.
 Symmetry of nucleocapsid

Icosahedral

Helical
 Soccer ball

Many viruses have a similar structure !

Icosahedral symmetry

Capsomers

20 faces / facets
(triangles)
12 vertices
Sides consist of hexon

Sides consist of pento

23
 Helical symmetry

Viral protein subunits

are bound to the viral
nucleic acids in a
periodic way
Steps in viral replication
 Steps in virus replication
Attachment

Penetration

Uncoating /disassembly

Synthesis of virus nucleic acids and p

Assembly

Release of virions
Virus replication some interesting facts

100 100,000 viruses/cell, 6

Average generation time 40 hours
6 to 40 hours

Number of virions /
infected cell 100 to
100,000

Much more than doubling

- dramatic exponential
growth !
Poliovirus
 Poliovirus pathogenesis
Virus begins to multiply in
the tissues around the
oropharynx /tonsils.

Enteroviruses are stable in

acid in the stomach

They pass to the intestines,

where they replicate

The virus begins to spill into

the Blood.
 Outcomes of poliovirus
infection
There are 3 possible outcomes of infection:
Subclinical infection (90 - 95%) - inapparent
subclinical infection account for the vast
majority of poliovirus infections.

Abortive infection (4 - 8%) - a minor

influenza-like illness occurs, recovery occurs
within a few days

Major illness (1 - 2%) - involves neuron

damage in the CNS (central nervous system)
 Poliovirus major illness
Spinal form: Paralytic disease may begin with
excruciating pain or spasms which may
precede paralysis of the extremities.

Bulbar form: An especially serious form is

bulbar polio as it involves respiratory center in
the medulla (Brain).
Poliomyelitis:

Iron lung machines

Iron lung wards
Influenza virus
 Influenza virus
8 RNA segments

Haemagglutinin ability to
bind to respiratory
epithelial cell

NA- increases disease

severity

Antibodies against HA /NA

protect /reduce severity
of disease
 NORMAL TRACHEAL
Normal MUCOSA
tracheal mucosa

3 DAYS
3 daysPOST-INFECTION
post infection 7 DAYS
7 daysPOST-INFECTION
post infection
Lycke and Norrby Textbook of Medical Virology 1983 36
Ramphal et al., INFECTION AND IMMUNITY 1979 25:992-997 (mouse)
 Where do new HA and NA
come from?
~18 types HA
~11 types NA
all circulate in
birds
Humans HA1-3;
HA5.
Humans NA1 and
NA2.

pigs
can be infected by
avian and human
influenza viruses

37
Pigs can act as host for generation of human-
avian reassortments

Influenza replicates in the digestive tract

of pigs and is shed in faeces

38
Reassortment in influenza virus
H1N1
N1
H1

H1 N2

H1N2

H2N2

N2

H2
Infection and disease
lecture 5

Rotavirus
Rabies
Ebola
VZV
HIV
Viruses and cancer
Emerging infections
Rota virus
 Rotaviruses - a major public health issue
Enterocytes
Gastroenteritis (diarrhea)

> 500 million infections

/year

>1.5 million deaths mostly

Asia / Africa

Targets enterocytes lining

the villi
 Rotavirus the disease
Enterocytes lining the tips of
intestinal villi are affected

Villous atrophy, death of Enterocytes

Enterocyte dysfunction net

secretion of intestinal fluid causes
diarrhoea

Role of NSP4 (non-structural protein)

as an enterotoxin stimulates
secretory pathway NSP4 is an enterotoxin
 Rotavirus transmission

Mainly person to person via fecal-oral route

Food and water-borne spread; Fomites

Large amounts of viral particles are shed in diarrheal

stools (1012 particles)

Infective dose is small as little 100 particles (virus

shedding 2 weeks).
Rabies virus
 Transmission
Usual route dog bite

Rare aerosol inhalation in caves (bats)

Rabies how does it cause disease ?

Note: no viremia

Murray et al., Medical Microbiology 8

 Rabies the disease
Disease occurs after 2-8 weeks (virus travels 6 inches in CNS /day)

- mental status varies: severe agitation / depression

- hydrophobia (most patients)
- spasms of larynx and pharynx may spit excessive saliva
- death often due to respiratory paralysis
- dogs can bite without provocation
What should you do if a dog bites you?

Wound soap / water / no sutures/

Vaccine

HRIG human Rabies Immunoglobulin at site

HRIG - injection
Ebola virus
Reservoir of Ebola virus
 Ebola virus pathogenesis
Human-to-human transmission
blood, body fluids , aerosol.

Ebola attacks connective tissue

it digests collagen, the protein

that holds the organs together.

The Ebola proteins chew up the

body's structural proteins

In this way, collagen in the body
turns to mush, tissues die and
liquefy
 Ebola The disease
Tremors /seizures

Blood smearing all over the

place

Transmission to new host.

The Ebola virus is

transmitted by direct
contact with the blood,
secretions and possibly
aerosol.
 Ebola virus - control
Upto 90% case fatality

Isolation of individuals

Awareness

Travel restrictions

Protection of heathcare
workers

No vaccine
Varicella zoster virus

(chicken pox)
 Pathogenesis - varicella
Respiratory route

Replicates in the regional

lymphnodes

Replicates in liver

viraemia skin , salivary

glands are seeded

From skin to neurons in the

spinal cord (Latent)
 Zoster (Shingles)

Reactivation of latent virus several years after primary infection

Zoster (Shingles)
 Zoster (Shingles)
Reactivation of latent VZV
Similar vesicular lesions
Often involves skin supplied by the infected part of the spinal
nerves
Occurs in >10% of individuals with a history of varicella
infections; often in IC hosts
Usually @ > 50 years
Trigger ?
 HIV (Human immunodeficiency virus)

Transmission blood / sexual /

vertical

HIV infects CD4+ T lymphocytes

and macrophages

Minor illness following

infection

HIV continues to replicate but

the immune system to keep the
virus to low levels for several
years. HIV infected T-lymphocyte
Progression from HIV infection to AIDS
After about 5-15 years the
body is not able to replace
the lost CD4+ cells

Virus loads increase and

CD4+ cells decrease (AIDS
Acquired immunodeficiency
syndrome)

The individual succumbs to

opportunistic infection
 HIV: Opportunistic infection

Account for disease and death in AIDS patients

Eg.
Fungi: candida species
Bacteria: mycobacterium avium-intracellulare
Viruses: cytomegalovirus

Death in about 1-2 years

Tumour viruses
History
 History

1966 Nobel for Rous

1980s HBV, HPV

About > 25% of all cancers are virus-related

 Cancer

Production of new cells

death of old cells

Cancer unchecked growth

of cells

Transformation of a normal
cell to cancer cell may take
several years

Clonal expansion of cancer

cells
 Tumour viruses
Both DNA / RNA viruses

Persistent infection

Virus proteins may interfere with the functioning of host proteins

Virus may /may not be actively replicating

Hit and run no virus in virus induced cancer tissue

Innocent bystander virus in cancer tissue; but has nothing to do

with the cancer
 Human papilloma viruses (HPVs)
Infect epithelial cells of skin

Common warts

HPV genital infections - STD

99% of cervical cancer cases

Anal cancer
Hepatitis B virus / hepatitis C virus

Chronic infection of
the liver

Major cause of liver

cancer
 Emerging and re-emerging
infectious diseases
Emerging infectious disease: Newly identified &
previously unknown mirobe that causes major
problems. Eg. Zika, Ebola

Re-emerging infectious disease: Infectious agents that

have been known for some time, had fallen to very low
levels that they were no longer considered a major
problem & but increasing numbers are now being
reported eg. Influenza virus, TB
 Factors leading to emergence / re-
emergence of infections
Drug resistance (eg. TB- re-emergence)

Evolution of the microbe (eg. HIV from SIV)

Displacement of animals

Humans populating areas close to animals

International travel