Specificity of human antibodies to oncovirus glycoproteins: recognition of antigen by natural antibodies directed against carbohydrate structures.

Abstract

Antibodies in human sera from healthy individuals were shown to be reactive with highly purified 70,00OA-totn envelope glycoprotein (gp70) of the simian sarcoma virus-simian sarcoma-associated virus (SSV-SSAV) complex in radioimmunoprecipitation assays under certain conditions. The specificity of the reaction was analyzed in absorption tests with normal human serum proteins, assays of viral gp7O antigenicity after exposure to exo-and endoglycosidases or trypsin, and carbohydrate hapten inhibition studies. On the basis of the results obtained in these experiments we have concluded that immune recognition of SSV-SSAV gp7O can be mediated by naturally occurring heterophil antibodies in human sera that are reactive by virtue of binding to the carbohydrate moiety of the viral gp7O molecules. The results are consistent with the idea that the antibodies in. question are elicited as a result of exposure to many natural substances possessing widely crossreacting antigens and are not a result of widespread infection of man with replication-competent oncoviruses.The potential role of oncoviruses in the development of some human malignancies, particularly leukemia, remains an intriguing and unresolved issue. There are reports in the literature that some human tissues contain proviral sequences and can express, depending on the assays employed, reverse transcriptase activity, virus-like RNA, viral proteins, and even morphological structures resembling virions (with or without associated infectivity). However, these findings must be considered together with negative data from other investigators seeking similar evidence (see reviews, refs. 1 and 2). In the absence of a clearly defined oncovirus of human origin, a number of investigators have approached this problem by investigating human sera for naturally occurring antibodies to oncoviruses of other species. The results obtained have varied from positive to negative or equivocal (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) For preparation of soluble radiolabeled viral 70,000-dalton glycoprotein (gp7O), purified virions were subjected to detergent lysis in a buffer containing 0.05 M NaCI, 0.02 M Tris-HCl (pH 7.4), 0.5% Nonidet P40, 0.5% sodium deoxycholate, and 10% Traysylol protease inhibitor (10,000 kallikrein inactivator units per ml) for 30 min at 370C. After the viral lysates were subjected to centrifugation at 100,000 X g for 60 min in a type 50 rotor, the supernatant fractions containing soluble viral proteins, including radiolabeled gp7O, were collected and stored at -70'C until used.Purification of gp7O after dialyzing the above proteins against the appropriate column buffer was accomplished (i) by phosphocellulose chromatography of the above lysates followed by either hydroxylapatite (21) or DEAE-cellulose chromatography (22) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

Heterophile binding of human antibodies to glycoproteins of retroviruses

“…Our conclusions agree with those of Barbacid et al (1980) and Snyder & Fleissner (1980). We think it important to provide data based on a solid-phase assay, which avoids the criteria devolved at precipitation assays.…”

“…6) (Kurth et al, 1977;Kurth & Mikschy, 1978). Our interpretation of this binding is, however, very difficult, and conforms with that offered in more recent work (Barbacid et al, 1980;Snyder & Fleissner, 1980 (Yamaga et al, 1977).…”

“…These findings have been reported in abstract (Russell et al, 1979). Similar conclusions have been reached in recent studies using radioimmuno-precipitation rather than solidphase assays (Barbacid et al, 1980;Snyder & Fleissner, 1980).…”

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

“…However, the epitopes responsible have been characterized in relatively few studies, and in some of the older reports, this seroreactivity turned out to be to carbohydrate antigens present on the viruses due to their production in nonhuman cell lines (31,455). Antibodies to HERV proteins have also been described, particularly in patients with testicular tumors (60,430) and melanoma (82), but such antibodies can also be present in healthy individuals (24,208).…”

No significant correlation between specific antibodies to mouse mammary tumour virus and human cancer

“…Such techniques cannot accurately distinguish specific and nonspecific reactions of sera. Some authors believe that most reactiveness of human sera against viral proteins could be accounted for by heterophilic antibodies that bind the carbohydrate moieties of viral glycoproteins (Barbacid et al, 1980;Snyder & Fleissner, 1980). Nevertheless, human sera have been reported to react with core MMTV proteins using radioimmunoprecipitation (RIP) and ELISA with purified MMTV proteins (Zotter et al, 1983;Dion et al, 1987).…”