Matt Gethers/20.380 HIV Project/Meeting Notes/4.5.08 Design Pitch and Other Issues

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4.5.08 Design Pitch and Other Issues

Agenda

  1. Refine the presentation.
  2. Decide if we want to pursue John's superinfection-protected white blood cell idea.
  3. Set up a time to talk to Jacquin Niles about all things red blood cell?
  4. Talk about the other parts of the project (modeling, in vitro, in vivo, IP, ...) so we all know what we're writing.
  5. Figure out how we want to compile everything once it's written.
  • Note: May want to schedule another meeting to discuss points 2 onwards.

Refining the Design Pitch

Design pitch script is here.


SIR White Blood Cells

Superinfection Resistant (SIR) cells could be another means of developing a viral trap except that the trap would necessarily utilize cells with a genome. That could be useful because you could further engineer cells to migrate to places in the body characterized by high viral count. SIR-mediated viral traps could migrate to wounds and possibly make the spread of HIV less likely.

"An HUT-78 cell clone (F12) chronically infected by a nonproducer HIV-1 variant (Federico et al., (1989) AIDS Res. Hum. Retroviruses 5, 385-396) is fully resistant to superinfection with HIV-1 or HIV-2. We demonstrate that, in spite of the down-regulation of CD4 receptors, superinfecting-HIV-1 and -HIV-2 cross the F12 plasma membrane (even in the presence of OKT4A monoclonal antibodies) but fail to complete retrotranscription." [1]

Key papers:

  1. Taddeo B, Federico M, Titti F, Rossi GB, and Verani P. Homologous superinfection of both producer and nonproducer HIV-infected cells is blocked at a late retrotranscription step. Virology. 1993 Jun;194(2):441-52. DOI:10.1006/viro.1993.1283 | PubMed ID:8503167 | HubMed [Taddeo]
  2. Federico M, Taddeo B, Carlini F, Nappi F, Verani P, and Rossi GB. A recombinant retrovirus carrying a non-producer human immunodeficiency virus (HIV) type 1 variant induces resistance to superinfecting HIV. J Gen Virol. 1993 Oct;74 ( Pt 10):2099-110. DOI:10.1099/0022-1317-74-10-2099 | PubMed ID:8409934 | HubMed [Federico]
  3. Federico M, Nappi F, Ferrari G, Chelucci C, Mavilio F, and Verani P. A nonproducer, interfering human immunodeficiency virus (HIV) type 1 provirus can be transduced through a murine leukemia virus-based retroviral vector: recovery of an anti-HIV mouse/human pseudotype retrovirus. J Virol. 1995 Nov;69(11):6618-26. PubMed ID:7474070 | HubMed [Federico2]
  4. Nethe M, Berkhout B, and van der Kuyl AC. Retroviral superinfection resistance. Retrovirology. 2005 Aug 18;2:52. DOI:10.1186/1742-4690-2-52 | PubMed ID:16107223 | HubMed [Nethe]
  5. Wildum S, Schindler M, M√ľnch J, and Kirchhoff F. Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J Virol. 2006 Aug;80(16):8047-59. DOI:10.1128/JVI.00252-06 | PubMed ID:16873261 | HubMed [Wildum]
All Medline abstracts: PubMed | HubMed

Potential road blocks - The idea of SIR cells has been around for some time, so it's likely there's some IP associated with it. I imagine most people would have tried to make the human body generally resistant to HIV infection (vaccine?) rather than trying to create viral traps, but who knows? Also not sure what the "fail rate" of superinfection is.