1

WHY HERPES VIRUSES?

Specific Application:

May be used as an early predictor of

impending medically significant changes in

the immune response.

Herpesviruses are:

1. The most readily recognized latent viruses.

2. Ubiquitous and represent important

infectious disease risks with oncogenic

potential.

3. Not mitigated by preflight quarantine. Space

flight stress alters immune response.

4. Diminished immunity results in reactivation

& shedding of latent viruses

2

SPACEFLIGHT IS A

STRESSFUL

ENVIRONMENT

Various stressors associated with

spaceflight acting through the

hypothalamus-pituitary-adrenal

(HPA)-axis is the basic mechanism

involved. The HPA (brain and

adrenal glands)-axis responding to

stress increases the amount of

stress hormones such as cortisol

from the adrenal glands, and the

resulting reduction in cellular

immunity allows the viruses to

emerge from their latent state into an

active infectious agent.

3

SPACE ANALOGS

Bed Rest Closed

Chamber

Antarctica

4

Space Shuttle EBV Copies

0

200

400

600

800

1000

EBV Frequency: 29%

EBV copies 40+ 2

200-140 139-60 59-1 1-30 31-45

EBV Frequency: 16%

EBV copies 44+ 5

n = 32

Space Flights = 10

Control

n=18

Frequency: 3%

Copies: 40

EB

V C

op

ies p

er

ml S

ali

va

Days Before Launch

Pierson et al., Brain Behavior & Immunity, 2005

Frequency:16%

copies 417+ 31

8-14 2-4 5-7

Days of Flight Days After Recovery

5

SPACE SHUTTLE: CMV FREQUENCY

Astronauts Control

0

5

10

15

20

25

30

n = 71

n = 61 % C

MV

Posi

tive

Uri

ne

Sa

mp

le

6

7

OUR SALIVA ASSAY HELPED IN:

2. Early detection of Chicken

Pox (earlier mis-diagnosed)

* PBMCs and vesicular swab were also positive for VZV

Days After Treatment

0 5 10 15 20 25 30

0.01

0.1

1

10

100

1000

10000

VZV copies

Pain

Sa

liva

ry V

ZV

Co

pie

s

5

10

15

Pa

in

*

*

1. Early detection of Shingles

Mehta et al., J. Med Virology 2000

3. Corrected mis-diagnosis of shingles

8

MAJOR CONTRIBUTIONS OF SPACEFLIGHT

STUDIES TO PATIENT CARE

1. VZV can asymptomatically reactivate and shed in saliva.

2. VZV shed in saliva is infectious.

3. Shingles patients shed VZV in saliva and exhibit viremia.

4. Postherpetic neuralgia (PHN) patients can shed VZV in saliva for years.

5. Patients inoculated with Zostavax shed VZV in saliva for at least 28 days.

6. PCR can be used for rapid and unequivocal diagnoses of viral diseases –

prevents mis-diagnosis.

7. New possible etiology of chickenpox has been therorized.

9

4. Accurate diagnosis

results in effective

medication prescription

3. Doctor

analyzes

test results

2. Diagnosis based

on symptoms

and case history

2. Saliva sample is

tested for VZV DNA

RAPID, SENSITIVE, SPECIFIC PCR ASSAY FOR VZV

Standard Exam

1. Symptoms

checked, case

history considered

Some possibility of error

Exam with PCR Assay

1. Symptoms checked, case history

considered, saliva sample obtained

Almost no possibility of error

10

Saliva Collection and Processing

Old Method

Takes 6-7 Hours to complete

Saliva cotton swab

centrifuge 1400 x g, 5 min

centrifuge 8000 x g, 2/3 hours

extract DNA

quantitative PCR

New Method

Takes 1- Hour to complete

centrifuge 16,000 x g, 20 min

extract DNA

quantitative PCR

passive drool

pellet

synthetic swab

vortex 10 sec centrifuge 1400 x g, 5 min

DNA Yield vs. Cotton 15X 11X

Passive Synthetic Mehta et al., 2013

11

Scratch resistant lenses

Medical telemetry

Pain-control

Pacemakers

Flat panel TV

Fogless ski goggles

CCD – digital camera

Digital imaging of breast biopsy

Invisible braces

Solar energy

Plant research

Agricultural benefits

Smoke detectors

MRI

DVD

GPS, LED

Composite golf clubs

Astronomy

Programmable pacemakers

Miniaturization of computers

Robotics

Aeronautical advances for airlines

Memory foam mattresses & pillows

Infrared ear thermometers

Food Safety (HAACP)

Aeronautics (e.g., winglets)

EARTH BENEFITS OF SPACE PROGRAM

12

When friends and family call from

all over the world, they sound as if

they are right around the corner.

The scope, clarity, and reliability of

our long-distance telephone system

is the result of communications satellite

technology developed by NASA over

a 30-year period.

CAN YOU HEAR ME NOW?

13

SHUTTLE TECHNOLOGY HELPS

HEARTS

NASA Supercomputer experts teamed

with cardiologist Dr. Michael DeBakey to

develop a ventricular assist device to

function as a “bridge to heart transplant”

by pumping blood throughout the body to

keep critically ill patients alive until a

donor heart is available.

The battery-powered heart pump uses the

same technology used on the main

engines of the Space Shuttle.

14

MICROBE Shuttle Atlantis, STS-115, launch Sept 9, 2006

Salmonella enterica Typhimurium experimental design and results

In-flight

hardware

Wilson et al., 2007, Proc. Natl. Acad. Sci. USA. 104(41):16299-304; Wilson et al., 2008, PLOS One 3(12): e3923

* Synchronous ground controls maintained under identical conditions as those on-board Shuttle - ground and

in-flight hardware loaded with same sample.

Salmonella grown during spaceflight

displayed increased virulence in rich media Killed mice faster and killed mice at lower doses than identical

bacterial cultures grown on the ground

Virulence change dependent on the growth media

Salmonella grown during spaceflight altered

their gene expression 167 genes differentially regulated

Ion response genes/pathways

Identification of the global molecular regulator, hfq, (“master

switch”) of spaceflight induced cellular responses

Salmonella grown during spaceflight

showed the presence of a material

resembling a biofilm Biofilms are important in disease causing potential and vehicle

system failure