HIV Flashcards
HIV
Structure:
similar to transposable elements
Transposable element
– DNA sequence that can change position in the genome
Transposable element
Class 1 –
– retrotransposons, DNA → RNA (transcription), RNA → DNA (reverse transcription)
Transposable element
Class 2-
– DNA transposons, cut from genome by transposase and inserted elsewhere
Viral retro-elements
-in our genome (endogenous)
Gag – capsid proteins Pol – enzymes Env – envelope proteins
Properties
-enveloped, diploid RNA, lentivirus
GP – 160 composed of 120 and 41 which interacts with CD4 T cells/Macros
Core – cone shaped, capsid protein p24
Protein synthesis: precursor genes
Gag
Gag – matrix, capsid (p24), and nucleocapsid proteins
Protein synthesis: precursor genes
Pol
Pol – protease, reverse transcriptase, and integrase enzymes
Protein synthesis: precursor genes
Env
Env – envelope, gp120 and gp41 = gp160
Protein synthesis: precursor genes
Tat
Tat – activation of transcription
Protein synthesis: precursor genes
Rev
Rev – regulation of RNA splicing and mRNA export
Protein synthesis: precursor genes
Nef
Nef – cell activation signals, down regulates CD4, MHC1 (evasion)
Protein synthesis: precursor genes
Vif
Vif – viron infectivity, required to cause disease (blocks APOBEC)
Protein synthesis: precursor genes
Vpr
Vpr – G2 arrest
Protein synthesis: precursor genes
Vpu
Vpu – down regulation of surface CD4, virus release, anti-BST2
HIV
Mode of infection:
Receptors – Gp120 interacts with T cells/macros via CD4, CCR5 and CXCR4 – chemokine receptors
Gp41 undergoes conformational change to pull membranes together and allow fusion
Entry – partial uncoating → reverse transcriptase complex → convert RNA to dsDNA → Pre-integration complex (PIC) → enters nucleus → integrase cleaves ends and insert viral DNA into host genome
Transcription – Early – tat, rev, and nef proteins are expressed Late – structural – gag, gag-pol, env, vpu, vpr, vif
Maturation – cleavage of gag-pol with viral protease
Innate restriction factors:
host proteins to handle retrovirus replication, first line defense against HIV
Innate restriction factors:
APOBEC3
– G → A mutations, cytidine deaminases → incorporated into viral capsid → new virus is not infectious
Innate restriction factors:
BST2
BST2 – interferon-induced membrane protein, tethers virons to plasma membrane in the absence of vpu
Primary infection
– flu-like symptoms, CNS disorders, GI problems, lasts for a few weeks, high p24
Clinical Latency
– asymptomatic, constant viral replication and depletion of T cells, high T cell turnover rate
AIDS
<200 (A or B), opportunistic infections (C) and malignancy → death
AIDS Dementia Complex
– HIV invasion of the CNS by infected monocytes/glia
Encephalitis – perivascular cuffing, giant cells, glial nodules, astrocytosis, vacuolar myelopathy
HIV Lymphoid Interstitial pneumonitis
kids, alveolar macros fuse to form giant cells due to viral envelope GP
Opportunistic infections: treated
prophylactically
Opportunistic infections
Candidiasis
Candidiasis – CD4 T cells >200, most common fungal infection with HIV (presenting sign)
Opportunistic infections:
Pneumocystis jiroveci
Pneumocystis jiroveci - <200, pneumonia with immunosuppression → TMP-SMX
Opportunistic infections:
Toxoplasmosis, fungi
Toxoplasmosis, fungi - <100, undercooked meat and cat feces, CNS disease → TMP-SMX
Opportunistic infections:
Mycobacterium
Mycobacterium, asperg, MAC - <50 → clarithromycin and ethambutol
Opportunistic infections: Viral
Viral – CMV, EBV, HSV, JC
Opportunistic infections: Tumors
Tumors – Kaposi sarcoma, NHL, cervical carcinoma (HPV), CNS lymphoma (EBV)
Antiviral therapy:
inhibition of various enzymes and proteins
Antiviral therapy:
AZT
AZT – thymidine analog, inhibits reverse transcriptase
Antiviral therapy:
Protease inhibitors
Protease inhibitors – prevents maturation with cleavage of gag-pol → non-infectious immature virus
Antiviral therapy:
HAART
HAART – combined protease and reverse transcriptase inhibitors, used when CD4<350 or with AIDS defining disease
