Molecular cloning and expression of rhesus macaque and sooty mangabey interleukin 16: biologic activity and effect on simian immunodeficiency virus infection and/or replication.
Interleukin 16 (IL-16) has been shown to diminish HIV and SIV replication through inhibition of HIV and SIV mRNA transcription. To evaluate its role further, we compared IL-16 cloned from disease-susceptible rhesus macaques and disease-resistant sooty mangabeys. Recombinant rhesus macaque (rr) IL-16 was compared with recombinant sooty mangabey (rm), human, and other nonhuman primate IL-16 sequences and evaluated for its ability to induce chemotaxis and inhibit the mixed lymphocyte response (MLR). Also, rrIL-16 and rmIL-16 were evaluated for suppression of SIVmac251, which replicates efficiently in T cells and monocyte/macrophages (dual tropic), and cloned SIVmac239, which replicates efficiently in T cells (T tropic). Sequence comparison of rrIL-16 and rmIL-16 with human IL-16 showed >97% amino acid identity. Biocharacterization of rrIL-16 revealed potent induction of chemotaxis (p < 0.05) and marked inhibition of MLR (73 +/- 0.6%,p < 0.05) in rhesus and human cell systems. Using rrIL-16 and rmIL-16, p27 antigen production from PBMCs infected with SIVmac251 was decreased up to 70% (p < 0.05 and p < 0.01, respectively). In similar cultures infected with SIVmac239, rrIL-16 and rmIL-16 reduced p27 levels by 96 and 100%, respectively. These data demonstrate the biologic and antiviral functionality of rrIL-16 and rmIL-16.
Lee
M E
ME
Department of Pathology and Laboratory Medicine and the Winship Cancer Center, Emory University School of Medicine, Atlanta, Georgia 30329, USA.
Adams
J W
JW
Villinger
F
F
Brar
S S
SS
Meadows
M
M
Bucur
S Z
SZ
Lackey
D A
DA
Brice
G T
GT
Cruikshank
W W
WW
Ansari
A A
AA
Hillyer
C D
CD
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D016665:Cercocebus atys; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003001:Cloning, Molecular; D006801:Humans; D019410:Interleukin-16 / Q000235:genetics* / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D019410:Interleukin-16; D011994:Recombinant Proteins