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tissue, and circulating blood by standard virus isolation techniques. To determine whether the iso- lated virus exists in the form of an infectious virus- antibody complex, the anti-immunoglobulin neu- tralization technique should be used.

(3) Efforts should also be made to detect non- infectious virus-antibody complexes in the circu- lation. Upon incubation with the Clq component of complement or rheumatoid factor (Winchester et al., 1971), these complexes may precipitate out demonstrably. Conversely, incubation in an acid buffer may dissociate the complexes and permit the viral antigens and specific antiviral antibody to be identified as described in (1) above.

(4) If virus cannot be recovered by any of the above techniques, the animals should be immunized with isolated complexes and their sera tested for antibodies to a variety of viruses.

(5) When DNA-anti-DNA complexes are pre- sent in the glomeruli, an endeavour should be made to distinguish between viral nucleic acids and nucleic acids of nonviral origin.

(6)Since glomerulonephritis of differing degrees of severity can be produced in the same host by different viruses (e.g., LCMV versus LDV), attention should be focused on the factors involved in the initiation and production of immune-complex disease. It would be desirable to develop models to study the clearance of virus-antibody complexes from the bloodstream and the rate at which these complexes deposit and turn over in the kidney.

(7) Animals with infections characterized by per- sistent or recurrent viraemia (e.g., feline leukaemia, African swine fever, hog cholera, and avian lympho- matosis) should be examined for antiviral antibody circulating virus-antibody complexes, and immune- complex nephritis.

(8)A major effort should be made to elucidate the role of immune complexes in the pathogenesis of viral hepatitis in man.


In the last decade it has been shown that the transformation of cells by oncogenic viruses results in the appearance of new antigens on the cell sur- face and that immune responses to these antigens may be involved in tumour rejection. Non-onco- genic viruses can also produce new antigens on the surfaces of infected cells, but the biological signi-

ficance of these antigens has received relatively little attention. Evidence is now beginning to emerge, however, suggesting that the interaction of specific antiviral antibody and complement with surface antigens induced by non-oncogenic viruses can lead to cell destruction and may contribute to the patho- genesis of the lesions associated with certain virus infections.

In vivo, the best experimental evidence that anti- body can play such a pathogenetic role comes from the demonstration that the passive administration of specific antiviral antibody to animals infected with LCMV (Oldstone & Dixon, 1970), ADV, or Japanese B encephalitis virus produces or intensifies the charac- teristic lesions associated with these infections. In addition, it has been speculated that the interaction of specific antiviral antibody and complement with antigens induced by the respiratory syncytial, measles, hepatitis, dengue, and equine infectious arteritis viruses may be partly responsible for the pathological picture seen in these infections. Another suggestion has been that the passive attachment of virus, antiviral antibody, and complement to the surface of platelets or erythrocytes may result in cell injury and might give rise to some of the haema- tologic abnormalities associated with virus infections, such as dengue shock syndrome (Russell, 1971)— the most severe form of dengue haemorrhagic fever— and equine infectious anaemia.

The strongest evidence that antiviral antibody and complement can injure virus-infected cells has been produced by in vitro experiments. It has been shown that the infection of cells with viruses that do not produce cytologic injury (rabies (Wiktor et al., 1968), LCMV) (Oldstone & Dixon, 1971a), or with viruses that ultimately do cause cell damage (HSV, vacciniavirus, influenzavirus, Newcastle disease virus [NDV] (Brier et al., 1970) is followed by the appearance of new antigens on the surface of the infected cells and that the interaction of specific antiviral antibody and complement with these anti- gens can produce immunologic injury. In the absence of either specific antiviral antibody or com- plement, such injury does not occur. The degree of injury may depend on a number of factors (Brier et al., 1970), including (1) the density of viral antigens on the infected cell surfaces; (2) the inherent sus- ceptibility of the cells to lysis by complement; (3) the nature and concentration of the antiviral antibody; (4) the ratio of complement-fixing to non-complement-fixing antibody in the particular serum; and (5) the presence of inhibitors, such as

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