A previously undescribed species of human leukocyte, or alpha, interferon is present in the serum of many patients with systemic lupus erythematosus. It was shown to be alpha-interferon by neutralization with specific antiserums, affinity column chromatography, and antiviral activity on bovine cells. However, 23 of 30 interferon samples tested were inactivated by incubation at pH 2, a characteristic of human "immune," or gamma, interferon. Multiple samples of interferon from the same patient had similar biological properties, but samples from different patients were not all identical, suggesting that several variants of this species of human alpha-interferon may exist.

Several mechanisms have been put forward to explain how persistently infected virus-carrier cell cultures are maintained. In this report, information is summarized which suggests that selection of temperature-sensitive mutants may be involved in either establishment or maintenance of persistent infections both in cell cultures and in animals. The possible relation of this mechanism to other mechanisms of regulation of persistent infections is also discussed. Finally, a practical suggestion is offered to researchers and clinicians seeking endogenous viruses from cultured cells and tissues that may harbor temperature-sensitive variants.

Some immunologic parameters in homosexual patients with Kaposi's sarcoma (KS) or unexplained lymphadenopathy resemble findings in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Many patients with SLE have an unusual acid-labile form of human leukocyte interferon (HuIFN-alpha) in their serum. Sera from 91 homosexual men were tested for the presence of HuIFN. Of 27 patients with KS, 17 had significant titers of HuIFN in their serum. Ten of 35 patients with lymphadenopathy and three of four patients with other clinical symptoms also had circulating HuIFN. In contrast, only two of 25 apparently healthy subjects had serum HuIFN. All 32 samples of HuIFN had antiviral activity on bovine cells, a characteristic of HuIFN-alpha, and all of 14 representative samples tested were neutralized by antibody to HuIFN-alpha. In addition, the HuIFN-alpha in six of eight representative patients was inactivated at pH 2 and therefore appears to be similar to the HuIFN-alpha found in patients with SLE. These findings suggest that an autoimmune disorder may underly lymphadenopathy and KS in homosexual men.

Noncytocidal persistent infections at 37 C of mouse L cells (LX X) with infective B particles of vesicular stomatitis virus (VSV) could be established only in the presence of large numbers of defective interfering (DI) particles. Under these conditions, there was a rapid spontaneous selection of temperature-sensitive (ts) virus. At 10 days there was an increase to 17.8% in the frequency of ts clones in the virus population; by 17 days this frequency had reached 85.2%, and by 63 days 100% of the clones isolated were ts at 39.5 C, the nonpermissive temperature used. All 34 of the clones isolated from the 84-day fluid had an RNA-phenotype, and 8 clones that were tested all belonged to VSV complementation group I. When tested by an interference assay, L,,fluids did not contain significant numbers of DI particles (<1 DI/PFU). Furthermore, persistent infection of L cells at 37 C could be initiated under conditions in which few, if any, DI particles were present by using low input multiplicities (10-4 and 10-5) of a clonal isolate of an RNA group I mutant obtained from LX ,\ cells. On the basis of these and other results, a mechanism is proposed to explain the role of ts mutants in both the establishment and maintenance of the persistently infected state. MATERIALS AND METHODS Cells. Primary chicken embryo (CE) cells, mouse L cells (clone 929), and a line (BHK-21) of hamster kidney cells were propagated in Eagle minimal essential medium plus 4% calf serum. Viruses. The large-plaque mutant of VSVINI) (L,VSV) described by Wertz and Youngner (22) was grown in BHK-21 cells and assayed in CE cells. Monolayers in 32-ounce (ca. 950-ml) culture bottles were infected with less than 0.01 PFU/cell to avoid production of DI particles. This wild-type virus stock is referred to in the text as VSVe. Analysis of [PH1uridine-labeled viral particles by sucrose gradients failed to detect DI particles in lysates produced under these conditions. ts mutants of VSVINI) 90

The recognition that interferons (IFN)1 markedly affect a wide variety of immune responses has led to speculation that they may be involved in development of autoimmune diseases. Many patients with systemic lupus erythematosus (SLE) have high levels of circulating IFN (1-4). Since the IFN was inactivated at pH 2, it was originally assumed to be "immune" or gamma IFN (1). However, we recently demonstrated that the IFN in patients with SLE is not gamma IFN, but rather is an unusual acid-labile form of human leukocyte, or alpha, IFN (2, 3). A similar IFN was also found in patients with rheumatoid arthritis (3), autoimmune vasculitis (4), and the acquired immunodeficiency syndrome (5). In contrast, no IFN was detected in patients with drug-induced lupus (3), suggesting that production of IFN may be related to idiopathic immune disorders.Others found that SLE lymphocytes were poor producers of IFN in culture (6), but they neither characterized the IFN made in vitro nor measured serum IFN levels in their patients. We therefore re-evaluated IFN production by lymphocytes from SLE patients with and without endogenous IFN. We also quantitated the IFN-induced enzyme 2'-5'-oligoadenylate (2-5A) synthetase in cells from SLE patients. This enzyme is induced in cultured cells treated with IFN (7) and in lymphocytes from patients undergoing IFN therapy (8) or viral infections (9). The results suggest that most, if not all, SLE patients produce IFN that has biological significance, as demonstrated by elevated 2-5A synthetase in circulating lymphocytes.