1303. An Adipogenic Adenovirus Affects the Cytokine Pathways of Pre-adipocytes
Session: Poster Abstract Session: Viral Immunology and Pathogenesis
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Adenovirus serotype 36 (AD36) has been associated with obesity and infection of pre-adipoctyes with AD36 causes a more rapid accumulation of lipid.  We hypothesize that the anti-inflammatory and anti-apoptotic effects of AD36 play a role in the adipogenic process. We explored the early gene transcription and cytokine profile and responsiveness of infected pre-adipocytes.

Methods: In the first series, pre-adipocytes were exposed to AD36 and qPCR was performed for the E3 gene segments and mouse IL-6 gene at 1, 4, and 24 hours.  In the second series, preadipocytes were infected with AD36, AD2, or not infected and apoptosis was induced with TNF-a. Both a caspase 3/7 assay, and an Annexin V based assay were performed.  In the third series, infected cells were analyzed for TNF-Receptor.  In the fourth series, IL-6 concentration was measured from the supernatant of infected cells at 4 and 24 hours post-infection. 

Results: E3 gene transcription was detected as early as 1 hour post-infection.  Likewise, In AD36 infected cells, IL-6 gene transcription was 600% increased over uninfected controls at 1 hour (p<0.001). AD36 infected cells showed the lowest percentage of caspase 3/7 activation and apoptosis following exposure to TNF-a, although AD2 infected cells were still somewhat protected.  Analysis of TNFR-1 did not reveal any difference in fluorescence between AD36 infected and uninfected cells.  Concentrations of IL-6 at 4 hours post infection were 5.6 ng/ml (AD36), 3.8 ng/ml (AD2) and 0.089 ng/ml (control, p<0.05).  The concentrations of IL-6 in infected cells were found to be inhibitory to adipogenesis.

Conclusion:  The AD36 E3 gene segment encodes multiple genes which regulate the innate immune response.  We show that infection of preadipocytes with AD36 protects the cells from TNF-a mediated apoptosis.  TNF receptor removal from the cell membrane may not be important in this effect.  As with infected respiratory cells, pre-adipocytes respond with a robust IL-6 response to both AD36 and AD2.  All these effects occur within hours or infection, when the E3 gene is being transcribed, though no causation is shown here.  Future work to validate and explain these findings in the context of adipogenesis is needed.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

John Arnold, MD1, Erin Blevins, MD2, Annette Ilg2 and Christina Brown2, (1)Naval Medical Center San Diego, San Diego, CA, (2)Naval Medical Center, San Diego, San Diego, CA

Disclosures:

J. Arnold, None

E. Blevins, None

A. Ilg, None

C. Brown, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.