HIV and AIDS Flashcards
What does HIV stand for?
Human Immunodeficiency Virus
What does AIDS stand for?
Acquired Immune Deficiency Syndrome
Why type of virus is HIV?
Lentivirus (slow)
-HIV and AIDS both retroviruses
HIV transmission
Sexual contact Blood -blood contact -IVDU Infected blood products In utero Breast milk
Major route of HIV infection in developed countries
Male - homo/bisexual
Major route of HIV infection in developing countries
Male and female - heterosexual
Child - infected via in utero transmission
HIV types
HIV 1 - most common
HIV 2 - less easily transmitted and less pathogenic
Main groups of HIV 1
Main (M) - pandemic strains
New (N)
Outlier (O) - confined to Cameroon area
Many subtypes
HIV mutates readily
Reverse Transcriptase does not proofread
- ***** diagram
- infected individuals contain a heterogenous viral population
HIV evolution and origins
Likely chimp co-infection with 2 SIV strains
-viral crossover creates new strain
-how did it transfer to humans?
Origin of HIB-1 in Cameroonian Chimps –> Congo in 1920s –> urbanisation –> diamonds –> rail travel –> indipendence 1960s
HIV-2 confined to west Africa
HIV shape (DIAGRAM)
Lipid membrane of envelope, envelope glycoproteins, host proteins
Matrix protein
Major structural (core) protein
Single-stranded RNA, p7^gag, p9^gag, reverse transcriptase
Infection of CD4 positive cells (DIAGRAM)
E.g. Th-cell, gp120
- initial attachment via gp120 binding to CD4
- followed by co-receptor (CCR5/ CXCR4) binding
- attachment followed by membrane fusion and internalisation (gp41 dependent)
- when cells are activated viral proteins are produced and 1000s of new virus progeny synthesised
Resistance to co-receptor binding
People with CCR5 mutations are resistant
- occurs in 2-14% of Europeans (caucasian), and 15% of Icelandic
- heterozygous: < susceptibility to infection
- homozygous: resistance
Why so much resistance in Caucasian Europe?
Mutation is 3000 years old Evidence suggests not selection pressure Unlikely that it was Vikings Maybe Founder effect -spread from smaller population in which high frequency occurred
Virus variation during HIV infection
Isolates from early infection - CCR5 (M) -macrophage tropic and low cytopathic effect -more transmissable Isolates from late infection - CXCR4 (T) -high cytopathic ability -less transmissable
Infection and dissemination
Blood stream –> macrophage
- –> virus reservoir and transport –> dysfunction, virus release, cytokine release and dysregulation of immune functions
- –> CD4 cell, T cell –lymph node (increased viral load in blood–> CD4 cell cytolysis –> AIDS, dementia, immunodeficiency, loss of B-cell control (lymphadenopathy and hypergammaglobulinaemia), loss of DTH function (cutaneous infections, intracellular pathogens) –> loss of T-cell function –> severe systemic opportunistic infections, Kaposi’s sarcoma, lymphoma
Disease progression
Primary infection - 1000 CD$+ cells/ μl 3-6 weeks: acute HIV syndrome -dissemination of virus Clinical latency 12 weeks - 10 years 10 years: constitutional symtpoms, opportunistic infections 11 years: death
Opportunistic bacterial infections and AIDS
Mycobacterium tuberculosis
Salmonella
Haemophilus, Streptococcus, Pneumococcus- Pyogenic infections (pus formers)
-recurrent
Opportunistic protozoal infections and AIDS
AIDS-defining:
- Cryptosporidium (chronic diarrhoea)
- Toxoplasma gondii (disseminated, including CNS - from cats)
Opportunistic fungal infections and AIDS
Aspergillus - pneumonia AIDS-defining -Candida - oral presentation -Crytococcus neoformans - CNS -Pneumocystis jiroveci/ carinii - pneumonia
Opportunistic viral infections and AIDS
AIDS-defining:
- HSV: chronic oral infection
- EBV: hairy leukoplakia and B-cell lymphomas
- HHV-8: Kaposis sarcoma
Some oral manifestations of HIV infection
Thrush
Erythematous candidosis
Gingival erythema
Hairy leukoplakia
Progression to AIDS - untreated
10% of HIV-infected subjects progress within 2-3 years
5-10% clinically asymptomatic after 10 years
Remaining subjects progress to AIDS within 10 years - DEATH
Situation drastically improved by antiretroviral therapy
-low rates of AIDS and death compared to diagnoses in ART area
The AIDS epidemic
In UK most new infections among homosexual community (57.5%)
-39% hetero
-3% IVDU
-0.5% mother-child
Asian and African epidemic more heterosexual
-may be due to associated high level of STDs - ulceration