latest research, cd26 produced by the cell but does not enter bloodstream (at least they are not detecting any, levels lower than emitted by HIV infected cells) this is not good news as cd26 cleaves neuropeptide Y, if it is not cleaved it is neurotoxic (btw what about gluten??) NPY levels correspond to severity of CFS, so could be a good diagnostic bio/marker. she is very excited about all this. anyways results of a short search to see if there could be retroviral involvement in dp26 inhibition: ++++++++ Crystal structures of HIV-1 Tat-derived nonapeptides Tat-(1-9) and Trp2-Tat-(1-9) bound to the active site of dipeptidyl-peptidase IV (CD26). http://www.jbc.org/content/280/15/14911.long J Biol Chem. 2005 Apr 15;280(15):14911-7. Epub 2005 Jan 28.Weihofen WA, Liu J, Reutter W, Saenger W, Fan H.Institut fr Chemie/Kristallographie, Freie Universitt Berlin, Takustrasse 6, D-14195 Berlin, Germany. CD26 or dipeptidyl-peptidase IV (DPPIV) is engaged in immune functions by co-stimulatory effects on activation and proliferation of T lymphocytes, binding to adenosine deaminase, and regulation of various chemokines and cytokines. DPPIV peptidase activity is inhibited by both Tat protein from human immunodeficiency virus (HIV)-1 and its N-terminal nonapeptide Tat-(1-9) with amino acid sequence MDPVDPNIE, suggesting that DPPIV mediates immunosuppressive effects of Tat protein. The 2.0- and 3.15-A resolution crystal structures of the binary complex between human DPPIV and nonapeptide Tat-(1-9) and the ternary complex between the variant MWPVDPNIE, called Trp(2)-Tat-(1-9), and DPPIV bound to adenosine deaminase show that Tat-(1-9) and Trp(2)-Tat-(1-9) are located in the active site of DPPIV. The interaction pattern of DPPIV with Trp(2)-Tat-(1-9) is tighter than that with Tat-(1-9), in agreement with inhibition constants (K(i)) of 2 x 10(-6) and 250 x 10(-6) m, respectively. Both peptides cannot be cleaved by DPPIV because the binding pockets of the N-terminal 2 residues are interchanged compared with natural substrates: the N-terminal methionine occupies the hydrophobic S1 pocket of DPPIV that normally accounts for substrate specificity by binding the penultimate residue. Because the N-terminal sequence of the thromboxane A2 receptor resembles the Trp(2)-Tat-(1-9) peptide, a possible interaction with DPPIV is postulated. PMID: 15695814 [PubMed - indexed for MEDLINE]Free Article ++++++++ Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals. Clin Immunol. 1999 Jun;91(3):283-95. Hosono O, Homma T, Kobayashi H, Munakata Y, Nojima Y, Iwamoto A, Morimoto C. Department of Clinical Immunology, University of Tokyo, Japan. Abstract Human plasma contains soluble CD26/dipeptidyl peptidase IV (sCD26/DPPIV) although its physiological significance remains unclear. To determine whether the plasma sCD26 levels have clinical relevance in HIV-1 infected individuals, the concentration and DPPIV enzyme activity of plasma sCD26 were measured. While there is no significant difference between the plasma levels of sCD26 in 90 HIV-1 infected individuals and in 79 uninfected controls, specific DPPIV enzyme activity of sCD26 was significantly decreased HIV-1 infected individuals (P < 0.0001). Specific DPPIV enzyme activity was correlated with the levels of CD4+ T cells (r = 0.247; P < 0.02), CD8+ T cells (r = 0.236; P < 0.03), and adenosine deaminase (r = 0.227; P < 0.05) and had an inverse correlation with HIV-1 RNA (Spearman's r = 0.474; P = 0.0012). Furthermore, recombinant sCD26 enhanced the in vitro PPD-induced response of lymphocytes from HIV-1 infected individuals with decreased specific DPPIV enzyme activity. These results suggest that the specific DPPIV enzyme activity of plasma sCD26 may contribute to the immunopathogenesis of HIV infection. PMID: 10370373 [PubMed - indexed for MEDLINE] ++++++++ Role of CD26/dipeptidyl peptidase IV in human immunodeficiency virus type 1 infection and apoptosis. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC44937/?tool=pubmed Morimoto C, Lord CI, Zhang C, Duke-Cohan JS, Letvin NL, Schlossman SF. Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA. To examine the role of CD26/dipeptidyl peptidase IV (DPPIV; EC 126.96.36.199) in infection by human immunodeficiency virus type 1 (HIV-1), we utilized CD26 cDNA-transfected Jurkat T-cell lines. Both CD26- parental Jurkat cells and mutant CD26+ (DPPIV-) transfected Jurkat cells were readily infected with HIV-1, whereas wild-type CD26+ (DPPIV+) transfected Jurkat cells were more resistant to HIV-1 infection. Our results suggest that CD26 is not essential for HIV-1 infectivity as suggested by others but that DPPIV enzyme activity may decrease the efficiency of HIV-1 infection. Of great interest, we found that mutant CD26+ (DPPIV-) transfectants and CD26- parental Jurkat cells strongly expressed CD95 (Fas/Apo-1) and were more sensitive than wild-type CD26+ (DPPIV+) transfectants to the induction of apoptosis by anti-CD95 monoclonal antibody. These results suggest that CD26 may play a role in HIV-1-associated loss of -CD4+ cells through the process of programmed cell death.