Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry

Human immunodeficiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome, is cytopathic for CD4+ T cells and binds to these cells via a complex of the 110,000 m.w. viral-envelope glycoprotein, gp110, and the CD4 molecule. We treated virus with several physical, chemical, and enzymic agents to determine their effect on the capacity of HIV to bind to the CD4+ T cell line, CEM. Reduction and alkylation (but not alkylation alone) and trypsin digestion (but not glycolytic enzyme digestions) of HIV destroyed its capacity to bind. If the tertiary protein structure conferred by disulfide bonding is not disrupted, the tertiary and secondary conformations dependent on noncovalent forces appear to be thermodynamically favored, because treatment with denaturants such as sodium dodecyl sulfate, 8 M urea, alcohol, or heat (56 degrees C or 65 degrees C for 30 min) followed by removal of the denaturants did not affect binding. Irreversible denaturation and loss of binding occurred after heating at 100 degrees C for 10 min. HIV binding to CD4+ T cells was inhibited either by murine monoclonal antibodies to the CD4 molecule or by human polyclonal or murine monoclonal antibodies to the gp110 molecule. On the basis of results of binding inhibition obtained with a panel of alpha-CD4 monoclonal antibodies, the receptor site for virus on the CD4 molecule was mapped to the amino-terminal portion of the molecule. Four candidate alpha-CD4 monoclonal antibodies that were potent inhibitors of virus binding (OKT4A, OKT4D, OKT4F, and Leu-3a) were examined for the possibility that their binding sites (idiotopes) might share structural and conformational similarity with the CD4-binding site on gp110. Polyclonal human or rabbit anti-HIV sera (that reacted with gp110 and inhibited virus binding) did not react with or inhibit the binding of these four alpha-CD4 monoclonal antibodies. Conversely, rabbit anti-idiotypic sera raised against each of the four candidate CD4 monoclonal antibodies did not react with virus or inhibit virus binding to CD4+ T cells. Further search or different approaches may yet yield an idiotype that is a structural and conformational "internal image" of the CD4-binding site of virus.     

Modelling the impact of the regulation of estuarine drift‐netting on the declared rod catch of Atlantic salmon Salmo salar L. in the River Usk

1. A novel method was used to determine if the statutory regulation of drift‐netting at the mouth of the River Usk in Wales was associated with a significant improvement in the stock and rod catch of salmon in the river upstream.
2. A linear regression model was constructed, in which the annual rod catch of salmon declared from the Usk between 1977 and 1988 was the dependent variable and the simultaneous annual catch declared from the nearby River Wye was the independent variable. The model was extrapolated to project the annual rod catches of salmon on the Usk, relative to the Wye, between 1989 and 1995.
3. The model accurately projected the actual rod catches declared from the Usk in 1989, 1990 and 1991. However, between 1992 and 1995 the declared catches deviated significantly ( P ≤ 0.05) from those projected by the model. The upsurge in rod catches declared after 1992 from the Usk, relative to the Wye was concomitant with the regulation of estuarine drift‐netting.
4. It was concluded that diminished estuarine exploitation had a beneficial impact on salmon angling success on the Usk. However, the utility of the model was restricted by inconsistencies in the methods used to generate the data, by changes in fishery management policies and by a lack of essential information on the interrelationships between catch, effort, stock and environmental conditions.