RETROVIRUSES II

• "Trans-Activator of Transcription".

• Tat is a regulatory protein that drastically enhances the efficiency of viral transcription.

• Cellular Co-Factor

Cellular Co-Factor

• Cellular Co-Factor

• Rev is Essential for the Nuclear Export of Intron-Containing HIV RNAs

Rev is a transactivating protein that is essential to the regulation of HIV-1 (and other lentiviral) protein expression. A nuclear localization signal is encoded in the rev gene, which allows the Rev protein to be localized to the nucleus, where it is involved in the export of unspliced and incompletely spliced mRNAs. In the absence of Rev, mRNAs of the HIV-1 late (structural) genes are retained in the nucleus, preventing their translation.

• Cellular Co-Factor

• chromosome region maintenance 1

• CRM1 is also utilized by viruses at various stages of their lifecycle to mislocalize cellular proteins 

• CRM1-inhibition by Leptomycin B. Leptomycin B binds to CRM1 at Cys528 residing in

  its NES-binding groove and inhibits the binding of the cargo to CRM1

• Rev binds RRE (Rev-responsive element)

  vRNA and docks it to CRM1

• Cellular Co-Factor

ESCRT = endosomal sorting complexes required for transport

ESCRT complexes transport ubiquitinated cargo to cellular vesicles that bud directly into the cell's endosomal compartment, forming multivesicular bodies.

Cellular Restriction Factors

• TRIM5α Recognizes Incoming HIV Capsid

Cellular Restriction Factors

• SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV

• SAMHD1 Regulates Intracellular dNTP Pool (dNTP > dN +PPP)

• Lentiviral Vpx Proteins Target SAMHD1 for Degradation

Cellular Restriction Factors

• GBP2/5 Belong to the Superfamily of IFN-inducible

  Guanosine Triphosphatases (GTPases)

• GBP2/5 Reduces HIV Infectivityby Interfering With Furin-

  mediated Env Processing

• cellular restriction factor

• Type II Integral Membrane Protein

• Tethers (hält) Budding Virions at the Plasma Membrane

• CD317 is Antagonized by Different Viral Proteins

• cellular restriction factor

• Different Domains of SERINC3/5 Are Important for Their Antiviral Activity

• SERINC3/5 Affect HIV-1 Infectivity and are Counteracted by HIV-1 Nef

• cellular restriction factor

•  a Class of DNA Editing Enzymes

• APOBEC3s Induce G-to-A Hypermutation in HIV cDNA

• APOBEC3s are Antagonized by Lentiviral Vif Proteins (degradation)

• 
  

• Induction of ISG Expression —> Interferon-stimulated gene

• TRIM Proteins as Sensors of HIV Infection

'Bystander killing' is a term used to describe the broad cell death

• Pyroptosis

programmed cell death that leads to the release of mediators of inflammation and that is often triggered by recognition of pathogenic microorganism