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LV

HIV-1
HIV-2

Retroviruses
oncoviruses

adult T cell lymphoma
HTLV-1

tropical spastic paraparesis

HTLV-2

(disease?)

• widely distributed among animal species
HTLV-1:
• transmission - breast milk (mostly), also transplacental, sexual, IVDU, transfusions, transplants
• adult T cell lymphoma
• tropical spastic paraparesis - demyelination of the long motoneurons of the spinal cord
1) Cosmopolitan - worldwide
2) Melanesian - Melanesia, PNG, Australian aborigines
3) Zairian - Africa

HTLV-2 (rare):
• transmission - sexual, IVDU, transfusions, transplants
• no clear disease associations
Diagnosis of HTLV:
• EIA for antibody to HTLV-1/2
- confirm antibody with Western
PCR peripheral blood to distinguish between HTLV-1 and HTLV-2
•

HIV
env (gp120) --> CD4
env (gp41)

gag (p17)
gag (p24)
ssRNA
RT
lipid envelope

• global prevalence ≈ 34 million (plateau?)
• Africa - HIV-2

acute HIV
syndrome

clinical latency

AIDS

CD4+
cells

HIV RNA
(plasma)

weeks

mucocutaneous
entry
DC cells
capture HIV

years

chronic infection, trapped
throughout lymphoid tissue
- CD4+ cell count maintained
(production > destruction)

migrate to
lymph node

activation
- cytokines
- HIV envelope

‘presented’
to CD4+ cells
replication, spreads widely
throughout lymphoid tissue
high level
viraemia

• CD4+ depletion =>
- ↓CMI (Tc and suppressor T functions)
- ↓antibody responses
- disruption of cytokine production

accelerated replication
↑HIV, ↓CD4+ cells
immunodeficiency
systemic symptoms
opportunistic
diseases
death

gp120

CCR5
(cytokine
receptor)

budding

attachment CD4
and fusion
RT

assembly

DNA
RNA

translation
uncoating

genomic
RNA
integration

HIV-1
provirus

host TFs

env RNA
RNA splice
variants

activation

HIV seroconversion illness:
• develops in some patients ~ weeks after infection
• fever, lymphadenopathy, rash, arthralgia
• sometimes meningitis or neurological illness
• highly infectious during this stage
HIV Progression:
• most HIV patients are in the prolonged asymptomatic phase
- may be unaware of infection
- gradual decline in TH cells --> AIDS --> tumours and opportunistic infections
Opportunistic infections
• bacteria - TB
• parasites - Toxoplasma gondii
- Cryptosporidium parvum
fungi - Candida
•
- Cryptococcus
- Pneumocystis jirovecii
• viruses - HSV, VZV, CMV, HHV-8,
- HPV

Reactivation of latent infections:
• HHV-8 + AIDS --> Kaposi’s sarcoma
(tumour of lymphatic endothelium)

• T
...

• vertical
Sexual transmission depends on:
• frequency
• type (receptive anal - highest risk)
• barrier contraceptives
• level of infectivity
• ulcers

HIV testing
• initial screening - EIA - detect p24 and antibody (repeat)
• positive => supplementary assay - Ab Western (gold standard)
#
#
#
#
#
- p24 neutralisation

PCR for pro-viral DNA
gp120

gp41

p24

p17

positive Western =>
1 glycoprotein
+ ≥ 3 other bands

• note - infants born to HIV+ mothers will be IgG+

Ab+
Abindeterminate Ab+ - early genuine Ab
- false positive Ab
- HIV-2 band => Africa
--> serological follow-up
for 3 months

HIV antiviral therapy
• fusion inhibitors - block gp41 or CCR
• RT inhibitors - nucleotides, nucleosides, non-nucleosides (bind RT directly)
• integrase inhibitors
• protease inhibitors - prevent cleavage of viral proteins and formation of infectious virions
HAART (highly active anti-retroviral therapy)
= 2 nucleoside RT inhibitors + 1 of - non-nucleoside RT inhibitor
- integrase inhibitor
- protease inhibitor
- ↓ viral load (↓ 50 RNA copies / mL --> prolonged viral suppression and ↓ resistance)
- ↑CD4+ cells
- ↓ infections
- ↑ longevity
- ↑ quality of life
• resistance to antivirals eventually develops, requiring modification of therapy
- test for resistance by sequencing RT, protease genes => select appropriate new drugs



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