COD infectious diseases Flashcards
Describe AIDS
Acquired Immune Deficiency Syndrome WHO 2014: HIV prevalence among adults 15–49 years old • 38 million people infected • 33 million deaths since 1980s Incidence: • 2.6 per 1000 population 4th greatest cause of global deaths
What viruses is AIDS caused by?
2 viruses
HIV-1 = common
HIV-2 = less common (African)
What was the general clinical epidemiology of AIDS?
First 2000 cases (US) Homosexual men = 72% IV drug abusers = 17% Haitians = 5% Haemophiliacs = 1%
What sort of virus is HIV?
A retrovirus
Lentivirus
9kb RNA genomes
Converted to DNA upon infection
Integrated into host cell genome so it is a permanent infection
New viral RNA produced by host RNA polymerase
Lipid viral envelope also derives from host cell
What is the consequence of the HIV replication cycle?
T4 lymphocytes =
Helper cells =
Underpin normal immune function
B lymphocytes are stimulated to produce antibodies
Macrophages are activated to enter infected or damaged tissues
Other T cells are stimulated eg Cytotoxic killer cells
Assist in the elimination of cancer cells
Active HIV replication = depletion of T4 cell count
What are some Clinical signs & AIDS indicator diseases?
- Multiple and recurrent bacterial infections
- Mycobacterial infections
- Pneumocystis pneumonia
- Lymphoma
- Wasting, night sweats
How is HIV diagnosed?
ELISA
Detects circulating anti-HIV antibodies
• Positive 4 - 8 weeks after initial infection
What are some HIV drug treatments?
Antiretroviral protease inhibitors:
• HIV protease is essential
• Required for long protein processing
• Saquinavir
Entry inhibitors
• Bind CCR5 chemokine receptor
• Block HIV entry
• Maraviroc
Fusion inhibitors
• block HIV fusing with T4 cell membrane
• Enfuvirtide
Integrase inhibitors
• Inhibits the HIV integrase action
• Integration of viral DNA blocked
• Raltegravir
What is Antiretroviral Therapy (ART)?
ART prevents resistance (multiple drugs/cycled)
• Also most potent means of killing virus
Keep circulating virus low
• Less progression to AIDS
• Combinations of drugs are used
Describe HIV-1 RNA quantitation
• viral load assays • number of RNA genomes • correlates to number of viral particles in blood • statistical correlation: < 4530 copies of viral RNA/ml • clinically stable • slow progression to AIDS > 36, 720 copies of viral RNA/ml • rapid disease progression • early AIDS onset
Describe HIV-1 Therapy
Hit high viral load with sustained drug therapy
• Combined ART drugs
• Keep viral copies low (50 or less per ml serum)
What are viral load assays?
Quantitate HIV-1 RNA in blood plasma
• A surrogate marker for HIV treatment = viral burden/titre
• HIV RNA genomes equivalent to virus particle per mL blood
• Nucleic acid-based tests (NATs)
What is the best tool for HIV Molecular Epidemiology?
- HIV full length genome sequence
* Use phylogenetic clustering
What is the origin of HIV?
Related to Simian Immunodeficiency Virus (SIV) • Are chimpanzees the source? Multiple simian lentiviruses • HIV moved into humans Bush meat trade • Infected blood
While there is no cure for HIV infection, its preventable by:?
Interrupting transmission: surveillance, testing & counselling
• Interventions: Condom use & male circumcision
• Pre- & Post-exposure prophylaxis
• Blood donor screening
• Stop mother to child transmission
Describe coronavirus
Positive-single-strand RNA viruses
S: Spike → homotrimeric class I fusion glycoproteins
Two function: (i) Bind cell surface receptors and (ii)
induce fusion of viral and cellular membranes
• E: Envelope
virus morphogenesis, assembly and bud-ding
• M: Membrane glycoprotein
• N: Nucleocapsid
binds the RNA genome in a beads-on-a-string fashion
What is the life cycle of coronavirus?
Entry:
• Bind ACE2
• Need protease: TMPRSS,
cathepsin B and L
Viral gene expression: • Translation of ORF1a and ORF1b → polyproteins pp1a (nsp1–11) and pp1ab (nsp1–10) • Cleavage by two cysteine proteases nsp3 and nsp5