Task 3D Tissue Analogs for the Study of Varicella-Zoster Virulence and Infectivity (Completed)
Last Published:  07/27/17 09:48:12 AM (Central)
Short Title: VZV ROI
Responsible HRP Element: Human Health Countermeasures
Collaborating Org(s):
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Directed
Aims:
This study is concerned with determining if: VZV is alive, active and has the potential to spread.  These data also represent the potential for cases of Shingles and Ramsey Hunt Syndrome to be experienced by flight crews in long duration exploration.  VZV may assume increased virulence and/or live virus numbers in microgravity.  This study will demonstrate the sensitivity of the model and provide an operational deliverable in the form of a reliable test for live quantifiable virus.
Results Summary
Host cultures were also infected with a second herpesvirus again at low MOI, CMV (strain Ad169).  As both viruses are reactivated in microgravity by astronaut crews, they are particularly relevant to study. Each was inoculated from cell free stocks and the TLAs demonstrated greater sensitivity to the viruses than is normally seen in 2D cultures (MOIs of 1X10-1X100).  In aggregate, the proof of concept for the study of herpes viruses was realized by demonstrating conclusively that long term proliferation of herpesviruses can be accomplished in 3D TLAs without expiration of the host culture.  Additionally, the genome of VZV was surveyed in collaboration with Dr. Randall Cohrs at Univ. of Colorado and found to be intact as compared to VZV cultured in 2D cultures.  This was established by analyses of the virus which contained both GFP (Green Fluorescent Protein) and RFP (Red Fluorescent Protein) in different regions of the genome. Both critical sections of the genome were conserved.

• Gap analysis and recommended future studies or gap(s):
1. The NxPCM project believes this research demonstrates a novel ground analogue to mimic and study latency and the causative relationships associated with spaceflight viral re-expression events.  Additional ground analogues need to be identified to study other immune effects of spaceflight, therefore, the project does not recommend closure of Gap IM3 at this time.
2. Future studies using this analogue should be initiated to determine the precise mechanisms for the reactivation of latent viruses to better protect astronauts from outbreaks during spaceflight. 3D Tissue-Like Assemblies TLAs provide many of the native surface markers seen in actual human tissues.  Thus illumination of which markers are specific for viral transfer (e.g. EGF) would lead to possibilities for limiting cell to cell transfer.  Additionally, these TLAs allow the study of combinatorial physiological factors that cannot be studied in humans (due to ethical restrictions) or in animals as many of the herpes viruses are non-reactive or do not infect animal tissues at all (e.g. VZV and hCMV). Thus to study the reactivation event and persistent infection required human tissue.
3. The NxPCM project will re-assess the need for future gaps utilizing analogue environments upon the completion of the NEEMO Immune study.  No new gaps are recommended at this time.


Integration/Unique Aspects: TBD
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