25 - HIV and AIDS Flashcards
End stage disease caused by HIV
AIDS
Original name for HIV
Lymphadenopathy associated virus (LAV), then Aids associated retrovirus (ARV)
Three different stages in the formation and
maturation of HIV
- Polyprotein precursor
- Immature virion
- Structural rearrangement of the processed proteins in the mature virion
HIV genome and virion
- Enveloped
- +ssRNA with DNA intermediate
- Replicates using RdDp (RT)
- 2 copies of ssRNA codes for structural, regulatory, and accessory proteins
HIV structural proteins
Gag, Pol, Env
HIV regulatory proteins
Tat and Rev
HIV accessory proteins
Vpu, Vpr, Vif and Nef
Entry of HIV
Occurs largely across mucosal surfaces
Cells susceptible to HIV
Myeloid DCs, Plasmacytoid DCs, and Langerhans cells
DCs
Express high levels of C-type lectins, including DC-specific intercellular adhesion molecule 3 (ICAM3)-grabbing non-integrin (DC-SIGN)
DC-SIGN
- Glycoproteins
- Main HIV attachment factors at the surface of dermal and mucosal DCs
HIV Transmission
Can occur across the infectious synapse, exocytic pathway and de novo virus production
R5 variants
- Make up the majority of transmitted and founder viruses
- Predominates in the blood prior to the development of AIDS
T cell tropic strain of HIV
- X4
- Bind CXCR4
Macrophage tropic strain of HIV
- HIV R5
- Bind CCR5
Eclipse phase
- Infection of first cells
- Systemic spread via lymph
- IFN response
Acute phase
- First detection in blood
- Flu like symptoms
- CTL response
- Seroconversion
Chronic phase
- Viral set point established
- Progressive CD4 T cell loss
- Chronic inflammation
- Progression to AIDS
Higher set point
- More fit virus
- CTL escape
- HIgh levels of inflammation
Lower set point
- Poorly fit virus
- Strong IR
- Low levels of inflammation
AIDS
Presence of HIV infection and either a CD4+ T cell count of <200 cells per μl or an AIDS-defining complication
Effects of HIV-1 infection on lymphoid tissue
- Progressive damage to lymph node germinal centres
- Connective tissue replaces much of the normal cell population
- End result is increased viremia and decreased immune capacity
AIDS defining conditions
- Candidiasis of bronchi, trachea, lungs
- Cytomegalovirus disease
- Kaposi’s sarcoma
- TB
- Pneumocystis jirovecii pneumonia
- Toxoplasmosis of brain
Main classes of antiretroviral drugs
- Fusion inhibitors
- Entry inhibitors
- RT inhibitors (Nucleoside and non-nucleoside)
- Integrase inhibitors
- Protease inhibitors
HIV vaccine
- T cell mediated response
- Neutralising antibody response: Induce antibodies that block HIV in the blood, preventing HIV from infecting the body͛s cells.
- Non-neutralising antibody response: Induce antibodies that recognise HIV and recruit other immune cells to help destroy the virus.
- Combination responses
HIV prevention strategies
- Pre and post exposure prophylaxis
- Condom use
- Neutralising antibodies
- Male circumcision
- Vaccines
HIV persistance
- Throughout deep tissues with repopulation from multiple anatomical sources
- Blood is main source of dispersal
Requirements for protective immunity against HIV-1
- CD4 and CD8 T cells
- Innate immune responses
- NK CElls
- ADCC
- Neutralising antibodies
