Molecular Cloning and Expression of Rhesus Macaque and Sooty Mangabey Interleukin 16: Biologic Activity and Effect on Simian Immunodeficiency Virus Infection and/or Replication

Abstract

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.

Interleukin-16

“…Sequence homology for the secreted molecule comparing simian to human is Ͼ98%. Functionally, all simian-derived IL-16 has demonstrated the same bioactivities on human or simian T cells (chemotaxis, effects on a mixed lymphocyte reaction [21], and inhibition of HIV or SIV viral replication [21,22]), as observed with human IL-16. Murine IL-16 has also been isolated and sequenced [23].…”

“…The sequence, structure, and function of IL-16 are highly conserved in all species examined. Simian IL-16 has been cloned from Rhesus and Pig-tailed Macaque and Sooty Mangabey [21], as well as from African Green monkeys [22]. The simian IL-16 intraspecies homology for the whole IL-16 molecule is approximately 98%, whereas the homology compared with the human sequence is approximately 96%.…”

Immunization of Cats against Feline Immunodeficiency Virus (FIV) Infection by Using Minimalistic Immunogenic Defined Gene Expression Vector Vaccines Expressing FIV gp140 Alone or with Feline Interleukin-12 (IL-12), IL-16, or a CpG Motif

“…However, the supernatant from these cultures also contained strong chemotactic activity for T cells and monocytes. It was shown previously that exogenous IL-16 inhibits the replication of HIV, SIV, and FIV (3,47,51). The antilentivirus activity of IL-16 appears to be multifaceted.…”

“…This CD4 chemotactic cytokine is secreted by CD8 ϩ T lymphocytes, and the C-terminal 130-amino-acid portion will suppress HIV-1, simian immunodeficiency virus (SIV), and FIV replication in vitro (3,47,51,74). IL-16 is also involved in cell-to-cell signaling between DCs and T cells (39).…”

Molecular Characterization of Feline Interleukin 16: Chemotactic Activity and Effect on Feline Immunodeficiency Virus Infection and/or Replication

“…16,20 Concentrations higher than 100 ng/ml were less chemoattractant and may represent a phenomenon described earlier as high-dose inhibition. 16,20 In addition, specificity of rfIL-16 could be confirm ed by fIL-16-specific antibody-m ediated neutralization of chemotaxis (1:800 dilution, 110% migration; 1:1600 dilution, 264% migration).…”