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Thursday, June 07, 2007

Blood-Borne Viruses

11.5.07

• HIV.
• Hep B.
• Hep D.
• Hep C.
• Parvovirus etc.

AIDS
• Acquired Immune Deficiency Syndrome.
• First cases recognised in 1979.
• First paper 1981.

Does HIV cause AIDS?
Cons:
1. For each person with AIDS there are 99 who are HIV-infected.
2. HIV-positive AIDS cases (4 in total) - HIV is just another opportunist growing in AIDS patients.
Pros:
1. Cohort studies.
2. Therapy.

"AIDS viruses"
1983: Montagnier - Paris.
LAV (lymphodenopathy associated virus).
IDAV (immune-deficiency associated virus).
1983: Gallo - USA.
HTLV-III (human T-cell leukaemia virus III).
1984: Gallo.
HTLV-III (human T-cell lymphotrophic virus III).
1986: HIV-1 (human immunodeficiency virus-1).
HIV-2.

Retrovirus
Genome: RNA positive sense (2 copies per virion).
Envelope: Yes.
Capsid: Cuboidal.
Size: ~ 100-120 nm.

Classification
1. Spumaviruses.
2. B and D-type oncoviruses.
3. C-type oncoviruses.
4. HTLV-related oncoviruses.
5. Lentiviruses (SIV, HIV etc.).

HIV genes and proteins
GAG (Group specific antigen.)
Encodes capsid proteins. Made as long polyprotein and cleaved to p24,
p17, p15.
Pol (Polymerase.)
Encodes protease, reverse transcriptase, endonuclease/ligase.
Env (Envelope.)
Encodes envelope glycoproteins (gp). Made as gp160, which is cleaved to
gp120 and gp41.

Stages in infection
1. Attachment - 2 receptors.
2. Penetration - fusion/endocytosis.
3. Reverse transcriptase - produces provirus.
4. Integration.
5. Reactivation and new virus production.
6. Maturation - proteolysis.
7. Release - budding.

HIV - receptors
1. Initial binding by gp120 to CD4.
2. Conformational change to gp120 and gp41 exposes new ligand.
3. Ligand binds to chemokine receptors e.g. CCR-5.
4. Viral entry.

Cells infected
1. Lymphocytes (T-helper cells expressing CD4).
2. Monocytes and macrophages.
3. Brain cells (predominantly astrocytes and oligodendrocytes, but also neurones).
4. Enterocytes.
5. Laryngeal cells.

Human infection
1. Initial acquisition (sexual, blood etc).
2. Incubation period (4-6 weeks). Each day 109 - 1010 new virus particles produced (106 - 107 are mutant).
3. Seroconversion illness in only 50% of those infected. Resembles glandular fever.
4. Latent period (virus still excreted).
5. Development of AIDS. Rising viral load, falling CD4 counts.

HIV excretion
1. Semen.
2. Cervical secretions.
3. Blood.
4. CSF.
5. Breast milk.
6. Saliva.
7. Urine.
8. Faeces.

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