SIMIAN-VIRUS-40 FOOTPRINTS IN HUMAN LYMPHOPROLIFERATIVE DISORDERS OF HIV- AND HIV+ PATIENTS

SV40 sequences were investigated by PCR DNA amplification followed by filter hybridization in a series of human lymphoproliferative disorder s obtained from human-immunodeficiency-virus (HIV)-seronegative and HI V-infected patients. Our PCR and filter-hybridization conditions enabl ed us eo detect SV40 sequences in the range of 10(-4) to 10(-2) genome equivalents per cell. In non-Hodgkin's lymphomas (NHL) from HIV- pati ents, SV40 footprints were found in I I out of 79 (13.9%) samples, whi le in NHL from HIV+ patients SV40 DNA sequences were detected in 2/16 (12.5%). in Hodgkin's disease (HD), SV40 sequences were found in 7/43 (16.3%) and 1/12 (8.3%) in HIV- and HIV+ patients respectively. A slig htly higher prevalence of SV40 footprints was observed in reactive lym pho-adenopathies both in HIV- (3/9, 33.3%) and in HIV+ (6/17, 35.3%) p atients. Sequence analysis of 2 NHL and 2 HD DNA samples established t hat the amplified PCR products belong to the SV40 sequences. SV40 prev alence and load were similar in samples from HIV-seronegative and HIV- infected individuals, suggesting that SV40 probably does not undergo s trong reactivation phenomena in the context of HIV-related immunosuppr ession, Moreover, the large T-antigen(Tag) expression was detected by immunohistochemistry in 5/18 SV40-DNA-positive samples analyzed; howev er, few tumor cells (<1%) in 3/5 samples displayed positivity for SV40 Tag, while this viral oncoprotein was revealed in several reactive hi stiocytes present in all 5 SV40-positive tissues. These results sugges t that the lymphoid tissue could represent a reservoir for SV40 and ma y constitute the first seep in understanding whether this DNA tumor po lyomavirus has a role in the pathogenesis of human lymphoproliferative disorders. (C) 1998 Wiley-Liss, Inc.