How IFNs work

From JGV Direct
REVIEW: Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures
by Richard E. Randall and Stephen Goodbourn (pdf download)

Here's the latest paper I've been reading. Through out the courses that I have taken in college, I learned how viruses infect cells, and how our immune system works. Yet, of the immunology that we have learned, it's mostly aimed on the systems aimed on bacteria, parasites, and the ourselves (thus allergies), as these are the areas where most research studies have traditionally focused. As I am most interested in virology, the lack of info in courses on immunology against viruses seems like a gapping hole that I could not find a satisfying answer to in text books.

Now this review is the best that I have seen on the interferon (IFN) systems work against viruses. Although it's so comprehensive that most people might not understand all the things mentioned, it's really a very exciting read, and just by reading the parts that I could understand, I have already learned a lot. Here's some notes on the basics of the IFN response pathway:

Inducing INF activation

virus (dsRNA)
↓ ↓
IRF-3 & I-κB/NF-κB phsophorylated
↓ ↓
↓ 　I-κB ubiquitinated
IRF-3, NF-κB enters nucleus
↓
c-jun/ATF-2, IRF-3, NF-κB bind INF-βpromoter
↓↑(enhance)
INF-β→IRF-7→INF-α

*INF-α promoter only has IRF binding sites, no NF-κB site
*IRF-7 preexist in lymphocytes ->direct production of INF-α


INF downstream effects

INF-α/β(type-I)
　 ↓
common heterodimeric receptor ( IFNAR1 & IFNAR2 genes)
　↓ 　　↓
Tyk2　　JAK1
　↓ 　　↓
STAT2⇔STAT1(STAT complex)
　 ↓
+ IRF-9 to form the ISGF (STAT1/2 /IRF-9 complex)
　 ↓
bind IFN-stimulated response element (ISRE), present in promoters of most IFN-responsive genes