PMID- 18606648
OWN - NLM
STAT- MEDLINE
DCOM- 20080812
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 2
DP  - 2008 Jul 15
TI  - Medroxyprogesterone acetate inhibits CD8+ T cell viral-specific effector function 
      and induces herpes simplex virus type 1 reactivation.
PG  - 969-75
AB  - Clinical research suggests hormonal contraceptive use is associated with 
      increased frequencies of HSV reactivation and shedding. We examined the effects 
      of medroxyprogesterone acetate (MPA), the compound most commonly used for 
      injectable hormonal contraception, on HSV type 1 (HSV-1) reactivation and CD8(+) 
      T cell function in murine trigeminal ganglia (TG). In ex vivo TG cultures, MPA 
      dramatically inhibited canonical CD8(+) T cell effector functions, including 
      IFN-gamma production and lytic granule release, and increased HSV-1 reactivation 
      from latency. In vivo, MPA treatment of latently infected ovariectomized mice 
      inhibited IFN-gamma production and lytic granule release by TG resident CD8(+) T 
      cells stimulated directly ex vivo. RNA specific for the essential immediate early 
      viral gene ICP4 as well as viral genome DNA copy number were increased in mice 
      that received MPA during latency, suggesting that treatment increased in vivo 
      reactivation. The increase in HSV-1 copy number appeared to be the result of a 
      two-tine effect, as MPA induced higher reactivation frequencies from latently 
      infected explanted TG neurons in the presence or absence of CD45(+) cells. Our 
      data suggest hormonal contraceptives that contain MPA may promote increased 
      frequency of HSV reactivation from latency through the combinatory effects of 
      inhibiting protective CD8(+) T cell responses and by a leukocyte-independent 
      effect on infected neurons.
FAU - Cherpes, Thomas L
AU  - Cherpes TL
AD  - Department of Obstetrics, Gynecology, and Reproductive Sciences, University of 
      Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
FAU - Busch, James L
AU  - Busch JL
FAU - Sheridan, Brian S
AU  - Sheridan BS
FAU - Harvey, Stephen A K
AU  - Harvey SA
FAU - Hendricks, Robert L
AU  - Hendricks RL
LA  - eng
GR  - T32 AI060525/AI/NIAID NIH HHS/United States
GR  - P30EY08098/EY/NEI NIH HHS/United States
GR  - P30 EY008098-14/EY/NEI NIH HHS/United States
GR  - K23 AI064396-04/AI/NIAID NIH HHS/United States
GR  - R01 EY005945/EY/NEI NIH HHS/United States
GR  - T32 AI 060525/AI/NIAID NIH HHS/United States
GR  - R01 EY005945-22/EY/NEI NIH HHS/United States
GR  - P30 EY008098/EY/NEI NIH HHS/United States
GR  - K23 AI064396/AI/NIAID NIH HHS/United States
GR  - R01 EY05945/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Contraceptive Agents)
RN  - 0 (Cytokines)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/drug effects/*immunology/metabolism
MH  - Contraceptive Agents/*pharmacology
MH  - Cytokines/*immunology/metabolism
MH  - Female
MH  - Genome, Viral
MH  - Herpesvirus 1, Human/drug effects/genetics/immunology/*physiology
MH  - Medroxyprogesterone Acetate/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Tissue Culture Techniques
MH  - Trigeminal Ganglion/drug effects/immunology/*virology
MH  - *Virus Activation
MH  - Virus Latency
PMC - PMC2553693
MID - NIHMS51448
EDAT- 2008/07/09 09:00
MHDA- 2008/08/13 09:00
PMCR- 2009/07/15
CRDT- 2008/07/09 09:00
PHST- 2008/07/09 09:00 [pubmed]
PHST- 2008/08/13 09:00 [medline]
PHST- 2008/07/09 09:00 [entrez]
PHST- 2009/07/15 00:00 [pmc-release]
AID - 181/2/969 [pii]
AID - 10.4049/jimmunol.181.2.969 [doi]
PST - ppublish
SO  - J Immunol. 2008 Jul 15;181(2):969-75. doi: 10.4049/jimmunol.181.2.969.