The level of calmodulin increases in cells expressing HIV-1 envelope glycoprotein. Although a calmodulin increase is bound to alter many cellular metabolic and signaling pathways, the benefits to the virus of these alterations must be indirect. However, the possibility exists that increased cellular calmodulin benefits the virus by directly associating with nonenvelope viral proteins. We have, therefore, investigated whether calmodulin can interact with HIV structural proteins Gag, p17, and p24. Calmodulin binds Gag and p17 but not p24 in (125)I-labeled calmodulin overlays of SDS-polyacrylamide gels. Removal of calcium by addition of EGTA eliminates this binding. A computer algorithm for predicting helical regions that should bind calmodulin predicts that there are two calmodulin-binding regions near the N terminus of p17. Intrinsic tryptophan fluorimetry shows that two peptides, each of which includes one of the predicted regions, bind calmodulin: p17(11-25) binds calmodulin with a 2-to-1 stoichiometry and dissociation constant of approximately 10(-9) M(2), and p17(31-46) also binds calmodulin with a dissociation constant of about 10(-9) M. These binding sites are nearly contiguous, forming an extended calmodulin-binding domain p17(11-46). In H-9 cells, Gag and calmodulin colocalize within the resolution of confocal light microscopy.

SUMMARY In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p<002) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/M2 and 2-5 MU/M2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p

In a randomized controlled trial, 41 chronic hepatitis B virus carriers were allocated, by opening numbered computerized randomization envelopes, to receive recombinant interferon-alpha 2A at three different doses: 2.5; 5.0, and 10.0 mU per m2. Thirty-two patients received treatment (6 for 3 months, 26 for 6 months), and 9 patients were controls (received no treatment). Ninety-three per cent of our patients were homosexual, and 41% had anti-HTLV-III in their serum. None of the control patients lost HBeAg. In contrast, six of the anti-HTLV-III-negative patients (33%) responded to treatment (p less than 0.02): five of these responders were homosexual (p less than 0.05). The response rate was greatest (44%) in the anti-HTLV-III-negative patients who received 10 mU per m2 of recombinant interferon-alpha 2A. None of the anti-HTLV-III-positive patients responded to treatment. The percentage reduction of hepatitis B virus DNA was significantly less in the anti-HTLV-III-positive group in comparison to the anti-HTLV-III-negative group at 1 and 4 months of treatment and at 3 months after the end of treatment (p less than 0.05). These patients were younger (33 vs. 42 years, p less than 0.02), had lower mean baseline AST values (42 vs. 80 IU per liter, p less than 0.02) and tended to have milder histological disease. Homosexual men with HBeAg-positive chronic liver disease who are anti-HTLV-III-positive appear to be less responsive to the direct antiviral and immunomodulatory effects of recombinant interferon-alpha 2A. This may be due to the subclinical immunosuppressive effects of co-infection with HTLV-III.

No abstract