Download Interferons

CATEGORY: RECEPTORS & MOLECULES
INTERFERONS: TYPE I
Interferons: Type I
José Ignacio Saldana, Imperial College
London, UK
Figure 1. Increased
expression of MHC I
and viral antigen
presentation induces
CD8 T cell killing of
the infected cell or
protection from NK
cells if the cell is
uninfected
Interferon synthesis occurs primarily in response to viral single-stranded or double stranded
RNA. These RNA molecules are either the genetic material of RNA viruses or a product of viral
transcription that can be detected only after viral particles are degraded. In order to detect
these viral products, cells have develop specific recognition receptors present in endosomes
as it is there where degraded viruses are more abundant. One of the best described group of
receptors are Toll-like receptors (TLR) 7, 8 and 3. Upon binding to viral RNA, they induce a
signal that results in the production and secretion of interferons (see Figure 1). In addition,
there are other cytoplasmic RNA receptors, such as the retinoic acid-inducible gene I (RIG1), that are are also able to detect viral material outside of the endosome and induce interferon
synthesis.
Interferons contribute to the resistance against viral infection by binding to a common cell
surface receptor on the infected cell as well as on neighbouring uninfected cells. This triggers a
cascade of signals that end in the rapid transcription of several host cell proteins that contribute
to the slowing down of viral proliferation. One of these proteins is the enzyme oligoadenylate
synthetase (OAS) that catalyses the synthesis of specific 2’-5’ linked nucleotides that activate
a host ribonuclease that degrades viral RNA. Other products induced by interferons are the
protein Mx that drives resistance to infuenza virus as well as the serine-threonine kinase (PKR)
that mediates the inhibition of protein translation, restricting the production of viral proteins from
the the viral genome (see diagram of target cell; Figure 1).
Another way IFNα and IFN-β protect host cells against viruses is by triggering cellular immune
responses to these pathogens. Interferon stimulation of uninfected cells results in an upregulation of the MHC class I pathway of antigen presentation, favouring the specific
recognition and killing of the infected cells by CD8 T cells. Interferons can also activate NK
cells which in turn can release cytokines, induce inflammation and kill infected cells.
© The copyright for this work resides with the author
Viruses have adapted strategies to overcome and evade the immune system and, in response,
the host has evolved a broad range of strategies to ensure complete protection against viral
infection. One of these strategies relies on the production of proteins that interfere with viral
replication - stopping further transmission to, and infection of, neighbouring healthy cells. This
group of cytokines were named interferons due to their ability to “interfere” with the life cycle of
the virus and they are produced early during infection, even before other immune responses
begin. The two best characterised interferons are: IFNα, a family of closely related molecules,
and IFN-β which is a single gene product.