Oncogenic potential of human mycoplasmas was studied using cultured mouse embryo cells, C3H/10T1/2 (C3H). Mycoplasma fermentans and Mycoplasma penetrans, mycoplasmas found in unusually high frequencies among patients with AIDS, were examined. Instead of acute transformation, a multistage process in promotion and progression of malignant cell transformation with long latency was noted; after 6 passages (1 wk per passage) of persistent infection with M. fermentans, C3H cells exhibited phenotypic changes with malignant characteristics that became progressively more prominent with further prolonged infection. Up to at least the 11th passage, all malignant changes were reversible if mycoplasmas were eradicated by antibiotic treatment. Mycoplasma fermentans and Mycoplasma penetrans are the most common mycoplasmas associated with AIDS (1-3). M penetrans infects male homosexuals and is seroepidemiologically associated with Kaposi sarcoma (4). Wall-free mycoplasmas are among the few prokaryotes that can grow symbiotically and have a close interaction with mammalian cells for long periods of time without causing acute cytopathic effects. Thus, infections in cell culture are commonly unrecognized, and many persistent parasitic infections in humans or in animals are clinically silent (5,6). But what is the potential effect on mammalian hosts parasitically infected by the prokaryotes with seemingly low virulence? Can mycoplasmas, the simplest organisms capable of self-replication, alter significantly and permanently the biological properties of mammalian cells during the long course of persistent infection?In the 1960s, two studies reported that infection of mycoplasmas (Mycoplasma orale and one unspeciated) caused chromosomal changes (7,8). But the studies did not reveal that the cells underwent transformation. A separate study reported that introduction of mycoplasmas into cultures of baby hamster kidney (BHK) cells produced immediate morphological transformation with a higher soft agar cloning efficiency (9). Unfortunately, the BHK cells had a high rate of spontaneous transformation. In the 1980s, one article reported that an arthropod spiroplasma could rapidly transform mouse and monkey cells (10). Most scientists thought mycoplasmas simply introduced confusing artifacts that mimic cell transformation (11).Since the question of whether mycoplasmas can induce malignant transformation of mammalian cells may have great significance in general biology, tumor biology, as well as direct clinical implications, we have examined mycoplasmal transforming effects in the murine embryonic C3H/10T½/2 (C3H) cell system, pne of the few standard test systems available for studying potential carcinogenic agents or factors in animals or humans (12)(13)(14)(15). Using this model system with low inherent spontaneous transformation (12), we did not find mycoplasmas induced acute mammalian cell transformation described in the earlier studies. Instead, we found mycoplasma-mediated oncogenesis had a long latency and required a chronic pe...

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Epstein Barr virus (EBV) sequence variation is thought to contribute to Burkitt lymphoma (BL), but lack of data from primary BL tumors hampers efforts to test this hypothesis. We directly sequenced EBV from 12 BL biopsies from Ghana, Brazil, and Argentina, aligned the obtained reads to the wild-type (WT) EBV reference sequence, and compared them with 100 published EBV genomes from normal and diseased people from around the world. The 12 BL EBVs were Type 1. Eleven clustered close to each other and to EBV from Raji BL cell line, but away from 12 EBVs reported from other BL-derived cell lines and away from EBV from NPC and healthy people from Asia. We discovered 23 shared novel nucleotide-base changes in the latent membrane protein (LMP)-1 promoter and gene (associated with 9 novel amino acid changes in the LMP-1 protein) of the 11 BL EBVs. Alignment of this region for the 112 EBV genomes revealed four distinct patterns, tentatively termed patterns A to D. The distribution of BL EBVs was 48%, 8%, 24% and 20% for patterns A to D, respectively; the NPC EBV’s were Pattern B, and EBV-WT was pattern D. Further work is needed to investigate the association between EBV LMP-1 patterns with BL.

Coinfection with Mycoplasma fermentans (incognitus strain) enhances the ability of human immunodeficiency virus type-1 (HIV-1) to induce cytopathic effects on human T lymphocytes in vitro. Syncytium formation of HIV-infected T cells was essentially eliminated in the presence of M. fermentans (incognitus strain), despite prominent cell death. However, replication and production of HIV-1 particles continued during the coinfection. Furthermore, the supernatant from cultures coinfected with HIV-1 and the mycoplasma contained a factor that inhibited the standard reverse transcriptase enzyme assay. The modification of the biological properties of HIV-1 by coinfection with mycoplasma may be involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS).