Stephen Gould - Exosome Biogenesis and the Budding of Proteins and Viruses

Exosomes are small secreted vesicles that have a diameter of ~50-200 nm. Exosomes are enriched for a specific subset of host-derived proteins, nucleic acids, lipids and carbohydrates, though they also incorporate most host cell molecules at baseline levels. Various models of exosome biogenesis have been proposed, but the field lacks the robust mechanistic studies that are needed to obtain a molecular understanding of vesicle secretion. To shed light on this process, our laboratory has taken a cargo-based approach in which we focus on the cis-acting signals that are necessary and sufficient for the budding of specific proteins. These studies have revealed that exosomal proteins are targeted to sites of vesicle budding by a combination of (1) high-order oligomerization and (2) binding to the plasma membrane. In addition, our work supports the hypothesis that the plasma membrane is a major site of exosome budding. Interestingly, HIV and other retroviruses have the same topology, size, and array of host cell molecules as exosomes, raising the possibility that retroviruses bud from infected cells by an exosomal pathway. This hypothesis is supported by the fact that retroviral Gag proteins, their main structural protein, are targeted to sites of exosome budding, bud from cells in association with exosomal cargo proteins, form high-order oligomeric complexes that bind the plasma membrane, and require plasma membrane binding in order to bud from cells. Modeling HIV budding as an exosomal process has led to new lines of experimentation, new sets of data, and new interpretations of decades-old observations, all of which provide increasing support for the hypothesis that HIV and other retroviruses exploit the exosomal machinery to generate infectious viral particles.

[Vice]

I think that Gould and others should consider the likely explanation that there are no such things as retrovirus species with any kind of specific protein character(see the Perth Group on HIV-all their criticisms can be applied to retroviruses as a whole). Gould is on to something as far as exosomes go, but he does not need to presume the existence of a retrovirus. If you simply combine exosomes with differing toxicological/stress based factors you have a better explanation that fills some key gaps, for instance:

"Although the Trojan exosome hypothesis does not ex-plain the distinguishing pathologies caused by different retroviruses, it does offer a mechanistic basis for some of the most clinically important aspects of retroviral infection." Gould

A toxicological explanation fills that gap.

Also lulz at 48:30. Shows how compromised the NIH is and puts scientific funding in a very bad light by not following the evidence.

[antonimalachowski]

In conclusion, they have discovered the anus of the cell. That is the area from which the cell releases exosomal waste. Brilliant.

[CompuBOOT]

At the end of the day, nomenclature and infinite reductionism notwithstanding, the entire field of virology depends on whether the offending particles enter the body from outside the body, or whether the offending particles originate from inside the body and leave the body.

I'm not going to take the time to break down the following analogous elements (there are many and if you've got a good brain you can identify all of them) but suppose one were to make a video capturing the early morning putting out of garbage to curbside from inside the various houses and letting the garbage truck later take the garbage away.

Running the video forward, you got, by way of analogy, exosomes.

Now...

...run the same video backwards and you got, by way of the same analogy, viruses.