1.

Bacterial Virulence Factors and

Pathogenicity
Virulence= the degree of pathogenicity within a group or species of parasites
as indicated by case fatality rates and/or the ability of the organism to invade
the tissues of the host.
Some bacterial proteins (exotoxins) can elicit the features of a bacterial
infection when injected as pure proteins.
Vaccination with inactivated toxins (toxoids) led to a spectacular decline in the
incidence of many bacterial infections. Use to induce immunity to toxins
Antitoxins: Antibodies to toxin
Leading to the simplistic idea that all bacteria need to cause disease is a single
toxin... Commented [H1]: Ci ny nhm e ko son
Necessary for colonising and/or damaging tissues Molecular Kochs postulates
Delete gene, show loss of virulence in model system, add gene back, show
restoration of virulence.
Biochemical evidence of damaging potential NTTH-HCMIU-MM-2015
Distinguish pathogen from commensal bacteria
Comparative genomics
expressed or essential in vivo
Virulence as a process is
o MULTIFACTORIAL
A bacterial army needs more than just its firearms to enter and
secure enemy territory
o MULTIDIMENSIONAL
A programme of events organised in time and space
Virulence factors: Many factors determine the virulence of bacteria, or their
ability to cause infection and disease.
Inoculum Dose= Number of microbes-dose/ Number of pathogens at the
beginning of an infection
Greater dose, more chance infection will occur
ID50 or LD50 expresses virulence: Infectious or lethal dose for 50% of the test
population LD50 used for toxins
ID50 or LD50 is usually expressed as the amount of chemical administered per 100
grams (for smaller animals) or per kilogram (for bigger test subjects) of the body
weight of the test animal. Commented [H2]: This also
The LD50 can be found for any route of entry or administration but dermal
(applied to the skin) and oral (given by mouth) administration methods are the
most common.
LD01 Lethal dose for 1% of the animal test population
LD100 Lethal dose for 100% of the animal test population
LDLO The lowest dose causing lethality
TDLO The lowest dose causing a toxic effect
LC50 is the concentrations of the chemical in air/ water that kills 50% of the test
animals during the observation period (traditionally 4 hours). Commented [H3]: Ti e k hc lun
 TOXINS
Toxins are poisonous substances damage tissues; Cause shock, fever, inhibit
protein synthesis.
Toxins produced by bacteria are generally classified into two groups:
o Endotoxins: LPS of G-negative bacteria
o Exotoxins: Produced inside cell; Mostly proteins, kill in low concentrations;
Mainly gram positive; Gene on plasmids or phages; Not bacterial genes
Destroy part of cell or inhibit metabolic processes.
ENDOTOXINS OF GRAM-NEGATIVE BACTERIA
The endotoxins of Gram-negative bacteria are complex LPS (lipid A)
derived from bacterial cell walls and are often liberated when the
bacteria lyse.
Heat-stable and can be extracted
Pathophysiological effects: Similar regardless of their bacterial origin.
EXOTOXINS
Many G-positive and G-negative bacteria produce exotoxins of
considerable medical importance.

Toxic shock syndrome toxin - 1 (TSST-1)

All S. aureus responsible for menstruation-associated TSS produce TSST- 1. 50
% of the strains responsible for other forms of TSS produce TSST-1.
TSST1 is heat & proteolysis resistant and is superantigen.
Although the toxin has been associated with toxic shock syndrome, the
mechanism of action in unknown.
Chills, fever, weakness, diffuse red aches; Later shock and death
Activate blood clotting: Clots obstruct capillaries; Death of tissues-DIC
Info box: Septic Shock or Shock Sepsis

Sepsis: systemic response to infection manifested by 2 of:

Temp>38oCor<36oC
Heart Rate (HR) > 90 bpm
Respiratory Rate (RR) > 20 bpm or PaCO2 < 32 mmHg
WBC>12x109/L,<4x109/Lor>10%bandform
Septic shock: sepsis with hypotension despite adequate fluid
resuscitation, with perfusion abnormalities that could include, but are not
limited to, lactic acidosis, oliguria, and/or acute mental status.
Endotoxin shock sepsis
Exotoxin shock sepsis: Superantigens Commented [H4]: no

STAPHYLOCOCCAL TOXIC SHOCK SYNDROME (STSS)

associated with infection of mucosal or sequestered sites by TSST.
 fatal multisystem disease
2 types of STSS known:
o Menstrual associated STSS: S.aureus occurs in the vagina of
menstruating woman who uses highly absorbent vaginal tampons.
o Non menstrual associated STSS: S.aureus occurs in other sites like
surgical wound.
Info box: Some exotoxins can serve as.... Superantigens
Superantigens= Bacterial toxins provoke intense response
Stimulate nonspecifically T cells
T cells release cytokines

Fever, N & V, diarrhea

System wide effect with organ failure Commented [H5]: no

Exotoxins associated with diarrheal diseases

Vibrio cholerae toxin
Staphylococcus aureus enterotoxin
Otherenterotoxins - enterotoxins are also produced by some strains of:

Yersinia enterocolitica
Vibrio parahaemolyticus
Aeromonas species Commented [H6]: no

Staphylococcal enterotoxins

Enterotoxins: is responsible for manifestations of staphylococcal food

poisoning. It usually occurs when preformed toxin is ingested with
contaminated food. Incubation period- 2 to 6 hours.Clinical symptoms-
nausea, vomiting and diarrhoea. The illness is usually self limited, with recovery
in a day or so. Source of infection- food handler who is a carrier.

The toxin acts directly on the autonomic nervous system to cause the illness,
rather than gut mucosa.

Produced by 30 to 50 % of all S. aureus strains Comprised of 8 serologically

distinct enterotoxins exist (A-E, G- I) Stable to heating; Resistant to gastric &
jejunal enzymes Are superantigens

Antiphagocytic factors
 Many bacterial pathogens are rapidly killed once they are ingested by
polymorphonuclear cells or macrophages.
Some pathogens evade phagocytosis or leukocyte microbidical
mechanisms by adsorbing normal host components to their surfaces.
Components of cell wall: Mycolic acids in M. tuberculosis, resistant to
lysosomal enzymes grows well inside phagocytic vacuoles Commented [H7]: no

PROCESS OF INFECTION
Sex comes before disease acquire virulence genes
Sense environment and Switch virulence genes on and off
Swim to site of infection
Stealth avoid immune system
Strike-back damage host tissues
Subvert host cell cytoskeletal and signalling Stick to site of infection
Scavenge nutrients especially iron
Survive stress pathways
Spread through cells and organs
Scatter

2. Common bacterial pathogens Commented [H8]: ci ny c dn k bng so snh

1. Airborne Bacterial Diseases - Meningococcal Infections

Meningococcal disease, first described in 1805 when an outbreak swept

through Geneva, Switzerland, is a potentially life-threatening infection.
Expressed as either Meningococcal meningitis, or Meningococcemia
(resulting in rapid circulatory collapse)
5% to 10% of patients die, typically within 24-48 hours of onset of symptoms.
10 to 20% of survivors of bacterial meningitis may result in brain damage,
permanent hearing loss, learning disability or other serious sequelae
(aftereffects of a disease).
Meningitis can be caused by viruses, bacteria, fungi, and protozoa.
VIRAL MENINGITIS: Usually mild. Clears up within a week ortwo without
specific treatment. Also called aseptic meningitis.
BACTERIAL MENINGITIS: Much more serious. Can causesevere disease
resulting in brain damage and death.
Nearly 50 species of opportunistic bacteria can cause meningitis with
notable ones are Haemophilus influenzae,S. pneumoniae, Neisseria
meningitidis and Listeriamonocytogenes.
The causative agent, Neisseria meningitidis (meningococcus), was identified
in 1887, which is leading cause of bacterial meningitis in children and young
adults in the U.S( 2,400 to 3,000 cases each year in U.S);

Neisseria meningitidis
 Neisseria meningitidis (Gramnegativediplococcusbacterium) withmultiple
serogroups( A, B, C, D, 29E,H, I, K, L, W-135, X,Y, and Z).
Strains belonging to groups A, B, C, Yand W-135 are implicated most
frequently in invasive disease.

Epidemiological issues of the disease

Reservoir: Humans are the only known reservoir of N. meningitidis.
Mode of Transmission: Person to person through droplets of respiratory or
throat secretions; Close and prolonged contact e.g.,(kissing, sneezing and
coughing on someone, living in close quarters or dormitories (military recruits,
students), sharing eating or drinking utensils, etc.); not ascontagious as cold or
flu.
Incubation Period:
The incubation period is variable, 2-10 days, but usually 3-4 days
Infectious Period:
An infected person is infectious as long as meningococci are present in nasal
and oral secretions or until 24 hours after initiation of effective antibiotic
treatment.
Laboratory criteria for diagnosis:
Isolation of Neisseria meningitidis from a normally sterile site (e.g., blood or
cerebrospinal fluid (CSF) or, less commonly, joint, pleural, or pericardial fluid).

N. meningitidis infection: Clinical presentation

> 2 Years :
High fever, headache, and stiff neck. Other symptoms include nausea,
vomiting, discomfort looking into bright lights, confusion, and sleepiness.
Newborns and small infants:
Classic symptoms may be absent or difficult to detect.
In babies under one year of age, the soft spot on the top of the head
(fontanel) may bulge upward.
Infant may only appear slow or inactive, or be irritable, have vomiting, or be
feeding poorly.

Vaccines for meningococcal disease

_ Safe and effective vaccines exist against serogroups A, C, W135, Y.
_ Vaccines recommended for:
_ 11-12 year olds, with a booster shot at 16.
If child misses a vaccine, very important to get vaccinated before living in a
college dorm.
_ People traveling to certain countries.
_ Scientists working with N. meningitidis in a lab.

2. Foodborne & Waterborne Bacterial Diseases Cholera

V. cholerae is a saltwater organism & it primary habitat is the marine
ecosystem. The organism is a comma-shaped, gram-negative, aerobic
bacillus whose size varies from 1-3 um in length by 0.5-0.8 um in diameter.
 Vibrios are sensitive to low pH and die rapidly in solutions below pH 6;
however, they are quite tolerant of alkaline conditions.
Has nearly 200 identified serotypes based on O-antigen of the LPS. Only O1
and O139 are toxigenic and cause Cholera disease. 2 categories of O1
serotypes Classical and El Tor (2 major biotypes), which was first isolated in
Egypt in 1905. Currently, El Tor is the predominant cholera pathogen
worldwide. O139: Contained in India, Bangladesh
Its antigenic structure consists of a flagellar H antigen and a somatic O
antigen. It is the differentiation of the latter that allows for separation into
pathogenic and nonpathogenic strains.

PATHOGENESIS:
V. cholerae cause clinical disease by producing an enterotoxin that
promotes the secretion of fluid and electrolytes into the lumen of the gut.
The result is watery diarrhea with electrolyte concentrations isotonic to those
of plasma.
The enterotoxin acts locally & does not invade the intestinal wall. As a result
few WBC & no RBC are found in the stool.
SYMPTOMS:
Occur 2-3 days after consumption of contaminated food/water
Vomiting; Cramps; Watery diarrhea (1L/hour); No fever
Without treatment, death in 18 hours-several days
COMPLICATIONS:
If dehydration is not corrected adequately & promptly it can lead to
hypovolemic shock, acute renal failure & death.
Electrolyte imbalance is common.
Hypoglycemia occurs in children.
Complications of therapy like over hydration & side effects of drug therapy
are rare.
TRANSMISSION
Cholera has 2 main reservoirs, man & water. Animals do not play a role in
transmission of disease.
Cholera is transmitted by the fecal-oral route through contaminated water &
food. Person to person infection is rare.
The infectious dose of bacteria required to cause clinical disease varies with
the source. If ingested with water the dose is in the order of 103-106
organisms. When ingested with food, fewer organisms are required to
produce disease, namely 102-104.
DIAGNOSIS
Organism can be seen in stool by direct microscopy after gram stain and
dark field illumination is used to demonstrates motility.
Cholera can be cultured on special alkaline media like triple sugar agar or
TCBS agar.
Serologic tests are available to define strains, but this is needed only during
epidemics to trace the source of infection.
TREATMENT
 The primary goal of therapy is to replenish fluid losses caused by diarrhea &
vomiting.
Fluid therapy is accomplished in 2 phases: rehydration and maintenance.
Rehydration should be completed in 4 hours & maintenance fluids should
replace ongoing losses & provide daily requirement.
DRUG THERAPY: The goals of drug therapy are to eradicate infection, reduce
morbidity and prevent complications.The drugs used for adults include
tetracycline, doxycycline, cotrimoxazole & ciprofloxacin. For children
erythromycin, cotrimoxazole and furazolidone are the drugs of choice.
Drug therapy reduces volume of stool & shortens period of hospitalization. It
is only needed for few days (3-5 days).
Drug resistance has been described in some areas & the choice of
antibiotic should be guided by the local resistance patterns.
PREVENTION
Education on hygiene practices.
Provision of safe, uncontaminated, drinking water to the people.
Antibiotic prophylaxis to house-hold contacts of index cases.
Vaccination against cholera to travelers to endemic countries & during
public gatherings.
CHOLERA VACCINES
The old killed injectable vaccine is obsolete now because it is not effective.
Two new oral vaccines became available in 1997: A Killed & a live
attenuated types. Both provoke a local immune response in the gut & a
blood immune response.
Cholera vaccination is no more required for international travelers because
risk is small.

3. Soilborne Bacterial Diseases Anthrax

A zoonotic disease of cattle, sheep, and horses
Human infection results from direct contact with infected animals or animal
products
Spores can survive in the soil for decades
Most likely would be released as an aerosol
May be sent as powder/slurry resulting in limited number of exposed
B. anthracis:Non-motile; Non-hemolytic; Encapsulated; Gram-positive rod
Lab diagnosis: Gram positive bacilli on blood smear; Blood culture growth of
large grampositive bacilli; Growth on sheeps blood agar cultures
Pathogenesis
Spore enters skin, GI tract, or lung
Ingested by macrophages
Transported to regional lymph nodes
Germinate in regional nodes, mediastinum (inhalational)
Local production of toxins
Edema & necrosis
Bacteremia & toxemia
Seeding of other organ systems
Inhalational Anthrax
 Infectious dose - "conventional wisdom: 8-50,000 spores
Incubation period: 1- 5 days (up to 60)
Initial symptoms nonspecific (2-5 d): fever, malaise, sweat/chills;
nonproductive cough, chest discomfort; nausea, vomiting
Syndrome:
hemorrhagic mediastinitis/pleural effusion
rapid progression to severe respiratory distress with dyspnea, diaphoresis,
stridor, cyanosis
50% of cases may rapidly develop concurrent hemorrhagic meningitis with
bloody cerebral spinal fluid
septicemia, toxic shock/death occur within 24-36 hours after onset of
respiratory distress
Cutaneous Anthrax
Most common naturally occurring form (95% cases; 2000 worldwide)
Deposition of spore into skin usually at site of cut or abrasion; papule forms
Incubation period - 1-7 days
Papule enlarges into a 1-3 mm vesicle by second day; progresses to a
painless depressed black eschar in 3 to 7 days
Patient may have fever, malaise, headache, and regional
lymphadenopathy
Diagnosis based on clinical findings and culture/direct smears and FA of
fluid/lesions
20% case fatality w/o antibiotic treatment; rare with treatment
Updated treatment for patients without systemic symptoms and lesion not
on head or neck and not with extensive edema):
Ciprofloxacin 500 mg q 12 hrs
or Doxycycline 100 mg q 12 hrs
or Amoxicillin 500 mg q 8 hrs
Anthrax Post- Exposure Prophylaxis
Starting antibiotics within 24 hours after aerosol exposure is expected to
provide significant protection
Duration: 60 days with or without vaccine
Most effective when combined with vaccination
Antibiotics are still indicated even when fully immunized
Long-term antibiotics necessary because of spore persistence in lung/lymph
node tissue
Inhalational Anthrax Treatment
Early IV antibiotics and intensive care required
Mortality may still exceed 80%
Current treatment of choice:
Ciprofloxacin 400 mg IV q 8-12 h or
Doxycycline 200 mg IV x 1 then 100 mg IV q 12 and
one or two additional antimicrobials
Antibiotic treatment must be continued for 60 days as there is a high risk of
recurrence due to delayed germination of spores
Once clinical condition improves, oral therapy can replace parental
therapy
 4. Arthropodborne Bacterial Diseases Typhus
Rickettsia prowazekii
Obligate intracellular bacteria
Pleiomorphic rods
Susceptible to moist heat and dry heat
Transmission
Human body louse: Pediculus humanus corporis; Infective for 2-3 days;
Infection
acquired by feeding on infected person; Excrete R. prowazeki in feces at time
of
feeding; Lice die within 2 weeks
Louse feces rubbed into bite or superficial abrasions: Inhalation of feces
Sylvatic typhus: Flying squirrel
30 human cases in eastern and central U.S.
Humans or flying squirrel required for life cycle
Organism dies with louse
Not transferred transovarially
Host responsible for maintaining infection
No person-to-person transmission
Clinical Symptoms
Incubation: 7-14 days
High fever, chills, headache,cough, severe myalgia
May lead to coma
Macular eruption
5-6 days after onset
Initially on upper trunk, spreads to entire body
Except face, palms and soles of feet
Diagnosis
Initial diagnosis
Clinical signs and history
Laboratory tests not diagnostic
Confirmatory diagnosis
Culture
Serology
Biopsy
PCR

5. Sexually Transmitted Bacterial Diseases Chlamydia

Obligate intracellular coccoid parasites
contain DNA and RNA, and ribosomes
lack ATP, biosynthetic pathways
cell wall but peptidoglycan absent - use disulfide bonds
non motile; not transmitted by arthropods.
 incorrectly called the PLT (psittacosis-lymphogranuloma-trachoma) viruses
or Bedsonia or basophilic viruses,
Multiply in the cytoplasm of the host cell.
generally epithelial cells
Basophilic inclusions
The methods used to study Chlamydia are those of the virologist rather than
the bacteriologist.
The clinical features, pathogenesis, pathology and epidemiology of
chlamydial infections are similar to those of viral infections.
Three species:
C. trachomatis: Trachoma conjunctivitis; proctitis; urethritis; salpingitis;
Lymphogranuloma venereum
C. psittaci & C. Pneumoniae: Upper respiratory infection; Bronchitis;
Pneumonia
Chlamydia form two main ecological groups: A&B
Infect only humans
Subgroup A
trachoma, inclusion conjunctivitis, and lymphogranuloma venereum
Zoonotic Infections
Subgroup B
Respiratory tract infections
Lymphogranuloma venereum LGV
200 reported cases per year.
Incubation period is 5 to 20 days.
Lesion: Transient vesicles on penis or vagina that are often unnoticed and
patients do not usually seek medical advice.
Bilateral inguinal adenopathy with overlying erythema:
Groove signs: Pompart's ligament is preserved despite the involvement of
multiple inguinal nodes lymph node shows both necrosis and granulomatous
reaction (dimorphic necrotizing granulomatous reaction)
Treatment Chlamydia
Adults Conjunctival,urethral, cervical, rectal:
Azithromycin 1 gm x 1 dose
Doxycycline 100 mg BID for 7 days
Children < 45 kg, urogenital & rectal:
erythromycin 50 mg/kg/day in 4 doses for 10-14 days
Neonates (ophthalmia,
Ofloxacin 300 mg po BID for 7 days
Erythromycin 500 mg QID for 7 days
Amoxacillin 500 mg TID 7-10 days infants born to infected mothers):
erthromycin 50 mg/kg/day in 4 doses for 10-14 days
Chlamydia Antigens
Antigens: group specific & species specific
Major outer membrane protein (cysteine-rich)
Eucaryotic cell binding protein
Host response: damage to specific tissues
Laboratory Diagnosis
 Isolate the organism from infected tissue.
Inoculate the yolk sac of seven-day chick embryos
Inoculate McCoy human cells.
Characteristic cytoplasmic inclusion bodies in infected cells.

3. Viral structure and Classification, General

concepts on VIRAL INFECTIONS.

What are Viruses?

- A virus is a non-cellular particle made up of genetic
material and protein that can invade living cells
- Viruses are both living and non living
- They have some properties of life but notothers
- Forexample,Viruses can be killed, even crystallized like table
salt However, they cant maintain a constant internal state
(homeostasis).
- Viruses are smaller than the smallest cell
- Measured in nanometers
Viral Structure and Classification:
1. Virus Structure and Growth:
General properties of viruses:
- Rely on host cells: energy and materials needed
for replicating their genomes and synthesizing
theirproteins
- Exist in either intracellular or extracellularforms
- Virion = Infectious virus particle- the nucleic
acidgenome surrounded by protein coat (capsid) and
some cases other layers ofmaterial.
= extracellular form- no respiration or biosynthesis
- Virion is different from Viroid
Nature of the Virion- Morphology:

- The structure of virions are quite diverse, varying widely in

size, shape, and chemical composition
- Size: 17 nm 3000 nmdiameter
 - Basic shape: Rod-like orSpherical
- Protective Shell Capsid
Made of many identical proteinsubunits
Symmetricallyorganized
50% ofweight
Enveloped ornon-enveloped
Can have complex structure orsome enzymes
- Genomicmaterial
DNA orRNA
Single- ordouble-stranded
- Most viruses infect only SPECIFIChostcells

Typical virus particle structure:

(Protomer, Capsomer, Capsid)

Viral Capsids:
- Viral capsids (coats) are made of individual protein
subunits; individual subunits are calledcapsomeres.
- Functionin:
Packaging and protecting nucleicacid
Host cellrecognition

Protein on coat or envelope feels or
recognizes host cellreceptors
Genomic materialdelivery
Enveloped: cell fusionevent
Non-enveloped: more complex strategies &
 specialized structures
Viral Shape: Symmetrical structure:

Most common

- General shape is symmetrical structure

- Some may be helical shapelike the Ebola virus
- Some may be polyhedralshapes like the influenza virus
- Others have morecomplex shapes likebacteriophages
 Complex Viruses:

Lipid - containing virus:

Myxovirus- Influenza Virus

Viral genomes:
- Either DNA or RNA, single stranded or double-stranded,
linearor circular.
 - All viruses use the cells translational machinery. Viruses
mRNA mustbe generated and then can be translated
on the host cell ribosomes

DNA Genome

RNA Genome

The virus host - ecology:

- Three types of viralhosts:
Prokaryotes
Plants
 Animal
- Study viruses Use cellculture Commented [H9]: ahihi nguyn phn ny ti e k hc

Quantification of viruses:
- Plaque Assay:
Number of plaque-forming units number of virus
infectious units present in the originalsample
Efficiency of plating: less than electronmicroscope
technique
- Intact Animal Methods
Virussamplesat10xdilutionsensitiveanimals:deada
nd
liveanimalsateachdilutionistabulatedandcalculat
ed.
LD50= dilution at which half of the injected animals die

2. Viral Replication:
Viral attack:
- HOST specific: Viruses are very specific as to which species
theyattack
- Humans rarely share viral diseases with otheranimals
- Animal viruses usually have protective envelopes made
from thehost cell membrane
Overview of virus replication
1. Attachment to thecell
2. Entry/Penetration (injection) of viral DNA orRNA
3. Transcription/Translation/GenomeReplication:
Biosynthesis of new viral proteins and nucleic acids
4. Assembly (Maturation) of the newviruses
5. Exit/ Release of the new viruses into theenvironment cell
lyses)

Viral Attachment and Penetration Commented [H10]: no

* ATTACHMENT:
 - Virion (naked/ enveloped) has one or more proteins on the
outsidethat interact with specific cell surface components
calledReceptors
- Receptors= normal surface components of the host such
asproteins, carbohydrates, glycoproteins, lipids, lipoproteins,
or complex of these
- Mutation happened in either host or virion may affect
viralattachment
- The attachment of a virus to its host cell results in changes to
both the virus and the cell surface that result inpenetration.
* PENETRATION:
- All animal viruses must cross the plasma membrane. Some
are transported in the cytoplasm via microtubules. Some
must crossthe nuclear envelope usually via nuclearpore.
- In order to replicate, some virus proteins must also enter the
hostwith viralgenome
- Different viruses have different strategies for penetration
* For example: Tailed Bacteriophage Attachment and Penetration
- Bacteria that have cell walls are infected in a manner
different from animal cells (no cellwall)
- The most complex penetration mechanisms have been
found in viruses that infect bacteria. Ex: bacteriophage T4
infects E.coli
The Entrance of Virus:
 Production of New Viral Nucleic Acid and Proteins
- In order to replicate in the host, viral genome must be made
andvirus- specific proteins must besynthesized.
- Two categories of viralproteins:
Early proteins: Proteins synthesized soon after infection.
Theyare necessary for the replication of virus
nucleicacid
Late proteins: Proteins synthesized later. Include the
proteinsof the viruscoat.
- The synthesis of these proteins requires viralmRNA

Francis Cricks Central Dogma:

- Because of virus, we have to modified it

Assembly of a helicalnucleocapsid: Commented [H11]: no
 Assembly of an icosahedralnucleocapsid
- A protein shell-procapsid is contructed, a copy of the virus
genome enters the procapsid, which undergoes modification to
form the capsid
Viral Release (Exit)
a. Enveloped Virus : Budding
b. Non- enveloped/ Complex Virus: Exocytosis or Lysis and
Death of host cell (Cytopathic)
* For example: Replication cycle of ssRNAphages Commented [H12]: no

Viral Latency
- Some viruses have the ability to become dormant inside the cell
latent viruses.
- They may remain inactive for long periods of time (years). Viral
DNA which was integrated into host cell is called
provirus/prophage.
- They replicate together with the cells thus called Lysogenic
Cycle -->Later, they activate to produce new viruses in response
to some external signal --> Once a prophage cell is activated,
host cell enters the Lytic Cycle -->New viruses form & the host cell
lyses (bursts) and Virus said to bevirulent (deadly)
Examples: HIV and Herpes viruses
 The Lysogenic Cycle
Latency in Eukaryotes
- Some eukaryotic viruses remain dormant for many years in
thenervous systemtissues
- Chickenpox (caused by the virus Varicella zoster) is a childhood
infection.It can reappear later in life as shingles, a painful itching
rash limited to small areas of thebody
- Herpes viruses also become latentin the nervous system. A
herpes infection lasts for a personslifetime.
Genital herpes (Herpes Simplex 2)
Cold sores or fever blisters (Herpes Simplex1)
Virus restriction and modification by the host
- Animals can eliminate invading viruses by immune defense
mechanism and RNA interferencemechanism.
- Prokaryotes can destroy double-stranded viral DNA byhost
restriction endonucleases (RE)
- Some DNA viruses have overcome their hosts restriction
mechanism by modifying their own nucleic acids: Glycosylation
andmethylation.

General concepts on VIRAL INFECTIONS

1. Source of viral infection: Shedding virus ->susceptible

2. Viral Transmission/ Routes of entry

Transmission of viruses can occur through two pathways: horizontal and vertical
transmission. In horizontal transmission, viruses are transmitted among individuals
of the same generation, while vertical transmission occurs from mothers to their
offspring, such as Rubella Infection during first trimester -> congenital infection
syndrome.

3. Types of viral diseases

a. Localized or Systemic/ Disseminated

Localised infection means the infection is restricted to one small area only. An
infected cut or ulcer is an example of this. A localised infection can spread
and become systemic. (Systemic means it's in the blood stream and is
spreading/has spread through the body. Septicaemia is an example of a
systemic infection.)
 Disseminated infection is an infection that enters at a single point and then
spreads throughout the body, often affecting numerous organ systems.When
a local infection turns into a disseminated infection, it may be associated with
severe complications. (More over, Disseminated diseases may be more
difficult to treat than their isolated counterparts. For example, both
disseminated gonorrhea and disseminated herpes require far more intensive
treatment than localized genital infections. Oral and rectal gonorrhea,
however, also may require more intensive treatment than genital infections,
even those infections are not disseminated)
After entry into the body: viral infections can be localised, to the site of
inoculation e.g: Human papillomaviruses - skin (warts)or spread on the body
surface e.g. Rotavirus
Viral Dissemination:
occurs via the blood (viraemia) or lymphatic system
viruses may travel free in the plasma but usually hitch a ride with
monocytes or lymphocytes
a few viruses can spread via the nervous system eg. rabies
Many viruses have a predilection or tropism for particular
organs/tissues/specialised cell types
the basis for this:
an appropriate cell surface molecule to act as a virus receptor =
susceptibiliy
appropriate cell transcription factors to switch on viral genes, and/or cell
enzyme pathways to produce viral proteins = permissivity

b. Acute or Persistent

Persistent infections are characterized as those in which the virus is not

cleared but remains in specific cells of infected individuals. Persistent
infections may involve stages of both silent and productive infection without
rapidly killing or even producing excessive damage of the host cells

Latency period (also latent period), the time between exposure to a

pathogen, chemical or radiation, and when symptoms first become
apparent. Virus latency, the ability of a virus to remain dormant. Sleep
onset latency, the time it takes a person to fall asleep)

4. How viruses cause diseases

a. By damaging/killing cells outright
Ex: Poliomyelitis

the virus is cytolytic

destroy motor neurons in the spinal cord, and so causes paralysis
b. By inducing immuno-pathology =>The patients T cells attack and destroy
virus-infected cells =>Inflammation and cell death
c. By transforming cells => cancer
When a virus infects a cell, it expresses proteins that cause the cell to
proloferate and/or block apoptosis

Retroviruses can inactivate genes responsible for suppressing tumor

formation.

Cancer is multi-factorial: Oncogenic viruses are very common, only a small

% of people infected actually get cancer

Major viral cancers

- An estimated 20% of human cancers involve viruses: Cancer of the cervix

- Human papillomavirus: Benign warts; Cervical Carcinoma: Cancer of the liver
- Hepatitis C virus: Liver carcinoma: Certain leukaemias & lymphomas
- Epstein Barr Virus: Burkitts Lymphoma
- Human T-cell Leukaemia Virus (HTLV-1): Leukaemia: Kaposis sarcoma
- Human Herpes Virus 8 Commented [H13]: ko cn

5. Treatment and Prevention

a. Antiviral
- Attachment/ Entry
- Nucleic acid replication: eg. AZT, Acyclovir
- Virus protein processing: eg. protease inhibitors
- Virus maturation: Neuraminidase inhibitor (Tamiflu);
- Problems with antivirals:
Identification of virus-specific target.
Generation of resistant variants: this is particularly a problem with those
against HIV where the drug has to be used for prolonged periods of time
b. Vaccines and immunization
- Vaccine:
An attenuated virus is a weakened, less vigorous virus. Attenuate" refers
to procedures that weaken an agent of disease (heating).
A vaccine against a viral disease can be made from an attenuated, less
virulent strain of the virus. Attenuated virus is capable of stimulating an
immune response and creating immunity, but not causing illness
- Other Viral Treatments:
Using Interferon (IFN) which are naturally occurring proteins made by cells
to fight viruses.
Boosting our Immune system