| |
| author |
Marina Hahn
| | title |
Understanding the Innate Immune Response to Single-Stranded DNA and Parvoviruses
| | abstract |
The innate immune system utilizes proteins known as pattern recognition receptors
(PRRs) to detect microbe-associated molecular patterns and to lead to the production of
signaling molecules known as cytokines. DNA-sensing PRRs cyclic GMP-AMP
synthase (cGAS) and interferon-inducible protein 16 (IFI16) bind to viral double-
stranded DNA (dsDNA) and lead to the production of pro-inflammatory cytokines known
as type I interferons (IFNs). Previous studies have not shown the production of type I
IFNs in response to single-stranded viral DNA (ssDNA). However, due to the existence
of ssDNA viruses, the nature of ssDNA viral replication resulting in the production of
double-stranded viral DNA, and evidence presented in the literature of IFI16 colocalizing
and associating with ssDNA, we hypothesized that single-stranded viral DNA should
induce a type I IFN response. Furthermore, we hypothesized that adeno-associated
virus (AAV), a small ssDNA virus that delivers its DNA into the nucleus, should induce a
type I IFN response due to the fact that both IFI16 and cGAS can translocate into
nucleus, though this virus is typically thought to induce no immune response. We
investigated type I IFN responses to ssDNA by transfecting mature THP-1 cells with
ssDNA from vaccinia virus (VAC70). We also investigated type I IFN responses to AAV
by infecting mature THP-1 cells with different serotypes of AAV2. IFN responses were
determined by measuring transcripts of interferon stimulated genes (ISGs) utilizing RT-
qPCR. These findings show that ssDNA does induce an IFN response whether it is
delivered through transfection of ssDNA VAC70 or through infection with AAV. These
data have implications regarding the presence of unknown ssDNA sensors and clinical
relevancy for gene therapy delivery techniques utilizing AAV.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.S. (2020)
|
| advisor |
Dr. Brianne Barker
|
| full text | MHahn.pdf |
| |
