Warning sweet summer children this blog post is NOT for you. Typically, these blogs discuss clinically interesting medical conditions. Often these blogs contrast the current state of say HIV care, with the long winter decades ago when HIV was a death sentence. If you are young, and never lived through the long winter stop reading now. Drink a beer for July 4th while floating down a lazy river. Or since the blog is late and it is now up to Emmanuel Macron to save the “free world”, celebrate Bastille Day. You can’t “handle” this blog.
This blog post is exclusively for those of us who have already “seen too many winters” and experienced the bad old days of HIV first hand. This blog is for us Maesters high in our ivory towers telling the young Samwell Tarlys of the world they don’t work hard enough. We already discovered whatever they are excited about years ago. This blog is for “my people”. Stiff, grey-haired (mostly white) men.
In fact, I would never have thought to read and post about this scientific paper, if I hadn’t listened to a This Week in Virology (TWIV) podcast brought to the world by grey haired men and Kathy Spindler. This blog again is about any and every infection that the involves the immune system. Some infections are only controlled if a person has neutrophils (staphylococcal skin infects are the classic example here, pneumocystis protection requires CD4 T cells, streptococcal infections are classic with antibody levels are too low). But this blog often goes on and on about CD8 cells being bad. Well to correct and confuse people we present the other side of the story…..The TWIV episode that inspired this blog issue is #488 “Who nose if it will work in humans” (http://www.microbe.tv/twiv/twiv-488/). There is a rather LENGTHY but interesting “snippet” on how mumps is perhaps “not worth eradicating”, but that disease from mumps has already and likely will continue to be more symptomatic in older and older adults then in the past when older adults were immune. This is because the immunity from exposure to the mumps vaccine “only” lasts 16-50 years. AFTER that “snippet” though they discuss the “main” paper (SiRNA-Mediated Control of Virus Replication in the CNS is therapeutic and enables natural immunity to West Nile Virus1, (https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30098-2) Cell Host and Microbe). This paper demonstrates and dissects the mechanism by which a neuronally targeted siRNA against a viral protein can protect mice from lethal West Nile Virus (WNV) infection. There are several findings worthy of blog posts from this stellar paper, but here we will only focus the cooperative activity of different parts of the mouse immune system in conjunction with the siRNA in mediated protection from viral encephalitis.
Briefly, since the siRNA is against the WNV virus, perhaps one doesn’t need an immune response for protection as the antiviral RNA could in theory completely block the virus. This is clearly not the case. The fact that the siRNA needs “help” from the immune system was demonstrated by using immunodeficient mice in which the siRNA could delay but not prevent mortality. After establishing that adoptive transfer of splenocytes from mice that had already survived a WNV could “rescue” the immunodeficient mice, they went on to show that even though immune serum and perhaps other factors were also likely necessary at least CD8 cells were one critical component needed to protect, since depleting CD8 cells from the “rescue” splenocytes ruined the rescue. Similar antiviral CD8 responses are likely occurring in primary HIV infection3 although in that particular case the cells are likely both responsible for some symptoms, as well as controlling the virus.
Us old men are sometimes known for dogmatically pushing our views. The point for today is that at least today I acknowledged CD8 cells aren’t “all evil”. While this blog will continue to highlight efforts to use the CD4/CD8 ratio as an early biomarker of potential reversibly pathology, let it not be said that all this blog does is trash CD8 cells when too many exist. Just like the Lannisters have at least one “redeeming” members….apparently so does House CD8.