A 55 Kd nuclear antigen, designated PSL has been found using a human autoimmune serum. This antigen accumulates in the nucleus, during the S phase, transiently associates with chromatin and possesses a DNA-binding ability. It appears to be highly conserved among eukariotic species including mammals, birds and insects.

A human serum from a patient with an autoimmune disorder, previously characterized for its ability to specifically recognize a chromatin-associated PSL or p55 antigen, was found also to detect a 30-32 K polypeptide in the cytoplasm of human HeLa cells. This molecule is strictly cytoplasmic, does not cross react with nuclear PSL and is synthesized only during the S phase of the cell cycle.

Using a serum from a patient with an autoimmune disease, we have recently described a novel 55 000‐dalton antigen (p55) in the nucleus of several animal cells including human ones. This antigen, designated PSL, was not related to the previously defined antigens recognized by sera from patients with systemic rheumatic diseases (Sm, n‐RNP, SS‐B, Scl‐70). We have now found that p55 is associated with chromatin structures as it is released from the nucleus of mink cell fibroblasts by saline + DNase treatments. Analysis by sucrose gradient centrifugation of the nuclear material released in these conditions indicated that p55 co‐migrated with core histones. Meanwhile, p55 was absent from the residual nuclear matrices (achromatinic nuclei). Localization of p55 in synchronized cells was performed by indirect immunofluorescence and immunoprecipitation. P55 appeared to accumulate in the nucleus during the S phase. Finally, it was not recognized by an anti‐SV40 tumor serum that specifically precipitated the protein p53, which has been recently related to cell proliferation. Thus, PSL an p53, although apparently not antigenically related, appear to be implicated in the same step of the cell cycle.

Toyocamycin (TMC), an adenosine analog has been previously reported to inhibit both number and infectivity of retrovirus particles released by chronically infected cells (Bonar et al., 1970; Riman, 1971; Mauchauffé et al., 1979). We have previously shown that loss of infectivity could result from the incorporation of TMC in place of adenosine in the genomic 35S RNA (Larsen et al., 1979). This phenomenon is likely to impair the structure of the viral genome in such a way that reverse transcriptase cannot properly copy the template. Another consequence of the Toyocamycin action on the retrovirus particles released by analog-treated cells was their reduced content in envelope glycoprotein or gp70 (Mathieu - Mahul et al., 1979). In order to find the origin of this defect, which could also explain the loss of infectivity, viral polypeptides present in the cytoplasm of Toyocamycin-treated cells were analyzed by immunoprecipitation with specific antisera. The results indicated a diminution of the biosynthesis of the envelope glycoprotein and other GAG gene-related polypeptides. However, the gpr85env precursor was normally synthesized and processed into its final products (gp70 + p15E), which accumulated in the cells. These result make it likely that Toyocamycin has no specific effect on the virus replicative process in chronically infected cells but acts by deteriorating cellular functions, which are necessary to virus assembly. Indeed, it was found that a membrane fraction corresponding to smooth endoplasmic reticulum and Golgi apparatus was severely reduced if not totally suppressed in TMC-treated cells.

Lorsque des cellules chroniquement infectées par un rétrovirus sont traitées par la Toyocamycine, un analogue de l'adénosine, elles produisent des quantités réduites de particules virales non infectieuses et appauvries en glycoprotéine d'enveloppe (gp70). Pour découvrir l'origine de ce défaut, nous avons analysé, à l'aide d'antisérums spécifiques, les polypeptides viraux présents dans le cytoplasme de cellules traitées par la Toyocamycine. Les résultats indiquent que le taux de synthèse de la gp70 est fortement diminué, mais que son précurseur gPr85 est normalement synthétisé et clivé en ses produits finaux (gp70 + p15E), qui s'accumulent dans la cellule. Il est probable que l'analogue n'agit donc pas spécifiquement sur l'une des fonctions de réplication virale mais plutôt en altérant certaines fonctions cellulaires nécessaires à l'assemblage des particules virales. A l'appui de cette hypothèse, nous avons observé dans les cellules traitées par l'analogue une très nette diminution du réseau membranaire du réticulum endoplasmique lisse et de l'appareil de Golgi; ces structures sont impliquées dans le transport des protéines virales.

Antibodies present in sera of patients with auto immune diseases (systemic Lupus erythematosus, mixed connective tissue disease) were used to react with nuclear ribonucleoproteins (HnRNPs) from normal cells and cells infected with retroviruses. Only antibodies directed against Sm and RNP antigens precipitated particles with definite spectra of small nuclear RNAs (SnRNA) and proteins. No difference could be found between infected and uninfected cells, suggesting that virus replication is dependent on normal cellular fonctions.

The murine Eveline cell line chronically infected by Friend virus was treated with Toyocamycin (TMC), an adenosin analog and the virions released in the presence of the drug were examined for their RNA. It was found that 70S RNA which was synthesized incorporated Toyocamycin. However, its subunit structure and its poly (A) content were apparently preserved. This incorporation may explain loss of endogenous reverse transcriptase activity.