Download Microbiology 2 - Viral disease

MCD – Microbiology 2 - Viral disease
Anil Chopra
1. How are viruses transmitted?
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Viruses have to enter their hose, replicate inside it and disseminate to new hosts.
Hosts have certain kinds of defences:
o Non-specific defences
 skin, mucous membranes, acid pH, proteases
o Innate immunity
 Complement, NK cells, phagocytes, interferons, fever, inflammation
o Specific immune response
 Antibody, cytotoxic T cells
Viruses can be transmitted via the:
o Respiratory tract
 Influenza, mumps, measles, variola, varicella-zoster virus (VZV),
rhinovirus
o Skin
 Papilloma viruses (HPV), HSV-1 & 2, rabies (bites), yellow fever
virus (mosquito)
o Blood products
 HIV, hepatitis B virus (HBV), hepatitis C virus (HCV)
o Genital tract
 HIV, HSV-2, HPV 16 & 18
o Alimentary canal
 Polio virus, hepatitis A virus, rotavirus
There are various factors that affect the transmission:
o Particle stability
 Enveloped viruses are less stable. Usually spread by close contact.
Compare influenza in winter months with foot and mouth disease virus
(FMDV), Isle of Wight in 1980.
o Duration of virus shedding
 Short duration, needs higher virus titres. Contrast influenza with HSV1
o Virus concentration
 Rotaviruses may be shed at 1010 pfu / ml.
o Availability of new hosts
 Population size, e.g. measles virus
 Animal reservoirs, e.g. yellow fever virus
2. Outcome of infection: cell death, persistent infection, cell transformation / cancer
The outcome of the infection is affected by various things:
 Dose/amount of virus
 Route of entry and travel of virus
 Age, sex and physiological state of host
o HBV, greater chance of establishing chronic infection if infected as
neonate. Male > female.
o Epstein-Barr virus (EBV), asymptomatic as child, glandular fever as
young adult
o Chickenpox, more severe as adult than child
Cell Death
Persistant Infection
Cell Transformation/
Cancer
A local infection is one that only replicates locally and has a short incubation times
between infection and symptoms.
A systemic infection is one that goes through multiple phases and the virus spreads
through the whole body, either via the blood or the nerves. This causes severe infection,
and is only cleared by cellular immunity.
3. Give examples of different viruses associated with infectious disease in humans and
describe the way in which they cause
disease
4. Influenza virus antigenic shift and drift
Influenza Virus 
The reason that influenza causes new
epidemics is because of antigenic drift
and antigenic shift. This means that
previous immunity is of limited value
against the new strains of the disease. The
virus is 100nm wide.
Antigenic Shift
This is where 2 different forms of the
same virus infect the same host cell. The
RNA undergoes some reassortment and a
new strain is formed from the two different forms of the virus.
Antigenifc Drift
This occurs because of point mutations in the HA which accumulate with time; the H3
HA circulating now has a surface very different to the H3 HA that appeared in 1968.
Antigenic drift produces less dramatic epidemics than antigenic shift
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H5N1 influenza viruses are endemic in avian species, spread globally by migratory
birds
Transmitted to other birds, e.g. poultry industry, high density and high virus titres
Has transmitted to man in S. and S. East Asia
Very high mortality in man (>50%)
Human to human transmission not evident yet, but the virus may adapt. Serious threat.
5. HIV life cycle and epidemic
 The HIV epidemic started from 1981 when the first reports of homosexual men
having T-lymphocyte dysfunction. The first retrovirus was isolated at in Paris in 1983
and then another strain of it in west Africa in 1986.
 This continued to spread and by 1996 more than 28 million infected, 5.8 m had AIDS
(75% had died).
 >95% of AIDS is in developing countries
 There is no vaccine, no cure once infected,
without drugs death is the outcome.
 About 14,000 new HIV infections each day;
10 people infected each minute
 2,000 are in children under 15 years of age
 About 12,000 are in persons aged 15 to 49
years:
 50% are women
 50% are 15–24 year olds
 8,200 AIDS-related deaths each day; 6 deaths per minute
 Aids is a retrovirus, of subgroup lentivirus: ssRNA +ve, diploid.
 It is more complex than other retroviruses as it has extra regulatory genes.
 Transmission: sexual, intravenous drug abuse, mother to baby, contaminated blood
products
 The virus binds cells expressing CD4(T-helper cells) and a co-receptor CCR5
(macrophage tropic strains) or CXCR4 (T-cell tropic strains).
 There is however a polymorphism, which, if homozygous gives immunity to the host.
This is in the CCR-5 gene.
 When you are infected, there is a minor loss of CD4 cells, but then these return to
normal.
 There is then a long dormant asymptomatic period of up to 15 years, after which the
virus load increases and the numbers of CD4 and CTL (cytotoxic T-lymphocytes)
decline. Oppurtunistic infections then cause death.