PMID- 11799168
OWN - NLM
STAT- MEDLINE
DCOM- 20020222
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 76
IP  - 4
DP  - 2002 Feb
TI  - Administration of recombinant rhesus interleukin-12 during acute simian 
      immunodeficiency virus (SIV) infection leads to decreased viral loads associated 
      with prolonged survival in SIVmac251-infected rhesus macaques.
PG  - 1731-43
AB  - The ability of recombinant rhesus interleukin-12 (rMamu-IL-12) administration 
      during acute simian immunodeficiency virus SIVmac251 infection to influence the 
      quality of the antiviral immune responses was assessed in rhesus macaques. Group 
      I (n = 4) was the virus-only control group. Group II and III received a 
      conditioning regimen of rMamu-IL-12 (10 and 20 microg/kg, respectively, 
      subcutaneously [s.c.]) on days -2 and 0. Thereafter, group II received 2 microg 
      of IL-12 per kg and group III received 10 microg/kg s.c. twice a week for 8 
      weeks. On day 0 all animals were infected with SIVmac251 intravenously. While all 
      four group I animals and three of four group II animals died by 8 and 10 months 
      post infection (p.i.), all four group III animals remained alive for >20 months 
      p.i. The higher IL-12 dose led to lower plasma viral loads and markedly lower 
      peripheral blood mononuclear cell and lymph node proviral DNA loads. During the 
      acute viremia phase, the high-IL-12-dose monkeys showed an increase in CD3(-) CD8 
      alpha/alpha(+) and CD3(+) CD8 alpha/alpha(+) cells and, unlike the control and 
      low-IL-12-dose animals, did not demonstrate an increase in CD4(+) CD45RA(+) 
      CD62L(+) naive cells. The high-IL-12-dose animals also demonstrated that both CD8 
      alpha/alpha(+) and CD8 alpha/beta(+) cells produced antiviral factors early p.i., 
      whereas only CD8 alpha/beta(+) cells retained this function late p.i. Long-term 
      survival correlated with sustained high levels of SIV gag/pol and SIV env 
      cytotoxic T lymphocytes and retention of high memory responses against nominal 
      antigens. This is the first study to demonstrate the capacity of IL-12 to 
      significantly protect macaques from SIV-induced disease, and it provides a useful 
      model to more precisely identify correlates of virus-specific disease-protective 
      responses.
FAU - Ansari, A A
AU  - Ansari AA
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, Atlanta, Georgia 30322, USA. pathaaa@emory.edu
FAU - Mayne, A E
AU  - Mayne AE
FAU - Sundstrom, J B
AU  - Sundstrom JB
FAU - Bostik, P
AU  - Bostik P
FAU - Grimm, B
AU  - Grimm B
FAU - Altman, J D
AU  - Altman JD
FAU - Villinger, F
AU  - Villinger F
LA  - eng
GR  - 1R01 27057/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA, Viral)
RN  - 0 (HIV Antibodies)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - DNA, Viral/blood
MH  - HIV Antibodies/blood
MH  - Humans
MH  - Immunologic Memory
MH  - Interleukin-12/*administration & dosage/*genetics/immunology
MH  - Lymph Nodes/virology
MH  - Lymphocyte Activation
MH  - Macaca mulatta
MH  - Proviruses
MH  - Recombination, Genetic
MH  - Simian Acquired Immunodeficiency Syndrome/immunology/*mortality/*prevention & 
      control
MH  - Simian Immunodeficiency Virus/*immunology/isolation & purification/pathogenicity
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Viral Load
PMC - PMC135900
EDAT- 2002/01/19 10:00
MHDA- 2002/02/23 10:01
PMCR- 2002/02/01
CRDT- 2002/01/19 10:00
PHST- 2002/01/19 10:00 [pubmed]
PHST- 2002/02/23 10:01 [medline]
PHST- 2002/01/19 10:00 [entrez]
PHST- 2002/02/01 00:00 [pmc-release]
AID - 1494 [pii]
AID - 10.1128/jvi.76.4.1731-1743.2002 [doi]
PST - ppublish
SO  - J Virol. 2002 Feb;76(4):1731-43. doi: 10.1128/jvi.76.4.1731-1743.2002.