Lecture 16 (9B) - HIV Flashcards
Acquire Immune Deficiency Syndrome
• immune deficiency
- opportunistic infections (TB, Candida, pneumonnia)
- opportunist cancers (Kaposi’s sarcome, lymphoma, cervical cancer)
• wasting syndrome
- weight loss
- fatigue
• brain
- AIDS dementia
AIDS and … are caused by the same virus
SLIM disease
People living with AIDS in 2010
34 million
Proportion of adults living with aids in 2011 who were women
50
Children living with HIV/AIDS in 2011
3.4 million
People newly infected with HIV in 2011
2.7 million
Children newly infected with HIV in 2011
390,000
AIDS deaths in 2011
1.8 million
Sub-saharan Africa take the brunt
- in 2012 about 68% of all people living with HIV resided in sub-Saharan Africa, a region with only 12% of the global population
- sub-Saharan Africa also accounted for 70% of new HIV infections in 2012
HIV infection from
- unprotected sexual intercourse with an infected partner
- vertical transmission (mother to child - in utero, during deliver, breastmilk)
- injection drug use (rare infected blood-blood products)
Effect of HIV on life expectancy
- in 1970-1975 = around 50-55
- 1985-1995 = around 50-65
- 2005-2011 = 30-45
Origins of HIV
- HIV-1M - chimpanzee
- HIV-1O - gorilla
- HIV-2 - sooty mangabey
Origins of HIV - zoonotic transmission
trans-species
simian to human
Origins of HIV-1
from SIV cpz
• evidence: viral genetic homology, geography of viruses
• at least 3 transmission events gave rise to HIV-1 groups M, N, O
• the group M viruses are estimated to have entered humansin the 1930s
Origins of HIV-2
from SIV sm
• evidence - viral genetic homology, geography
Origins of HIV - multiple transfers
- HIV-1 groups M, N, O, P
- only HIV-1 group M became pandemic
• primate species with no natural SIV infection often show now symptoms or illness
the closest viral species to HIV
the primate retroviruses called simian immunodeficiency viruses or SIV
• thought that HIV evolved from a common ancestor as these viruses and at some point in evolution it made the species jump to humans by spontaneous mutation endowing it with the ability to infect human CD4 T cells by binding to CD4 and CCR5
HIV viruses mutated and given the ability to infect human
CD4 T cells by binding to the CD4 and CCR5 proteins
3 groups exist
each thought to have arisen via a separate chimpanzee-to-human transmission event
• group M
• group N
• group O
Group M
majority
• cause of the global HIV-1
• many strains: ABCD FGHJK
Group N
non-O/non-M
• only found in cameroon
• very few strains known
Group O
outlier
• found in cameroon, equatorial guinea and gabon
• very few strains known
HIV-2
- non-pandemic
- restricted to west africa
- suggests HIV-2 may be less efficiently transmitted than HIV-1
- less pathogenic than HIV-1
- HIV-2 infected persons seem symptom-free longer than persons with HIV-1
Composition of the HIV-1 virus
- envelope
- matrix
- capsid
- lipid bilayer
- encapsulated + membrane from cell + spikes
- RNA
The replication of HIV
- absorption to CD4 and co-receptor
- fusion with cell
- penetration
- reverse transcription
- integration
- transcription
- translation
- capsid assembly
- budding
- maturation
into cyto, RNA reverse transcribed to DNA, DNA into nucleus, replicated, into cell membrane and takes some of membrane with it
HIV binds to
CD4
and CCR5
HIV infection usually requires both
CD4 and a chemokine receptor to infect target cells
(CXCR4/CCR5)
• CXCR4 on lymphocytes
• CCR5 on lymphocytes and macrophages
Co-receptor use and HIV infection
the most important coreceptors used by HIV-1 in vivo are CXCR4 expressed on lymphocytes and CCR5 expressed on lymphocytes and macrophages
• T-tropic isolates use CXCR4
• macrophage tropic isolates use CCR5
• dual tropic isolates use both