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Human herpesvirus 8 (HHV-8, or Kaposi sarcoma [KS]-associated herpesvirus, KSHV) is a necessary but insufficient cause of KS, as KS develops in few HHV-8-infected persons. In sub-Saharan Africa, marked differences in the geographic distribution of HHV-8 and KS suggest that environmental cofactors influence HHV-8 transmission, control, and progression to KS. However, a direct comparison of HHV-8 prevalence estimates is complicated because studies used different serologic assays and analytic methods. We assessed HHV-8 seropositivity in several African countries with heterogeneous environments and varying KS incidence using a unified approach.HHV-8 antibodies were measured among 3196 adults (aged 20+ years) and 2404 children (aged20 years) from five studies in four sub-Saharan countries in Africa. Serum samples were tested by the same laboratory using K8.1 and orf73 enzyme immunoassays.Children's HHV-8-seropositivity ranged from 18.1% in Kampala, Uganda, to 33.8% in North Mara, Tanzania, increasing steeply with age in all populations. Among adults, HHV-8-seropositivity ranged from 23.5% in Nigeria to 70.6% in rural West Nile, Uganda. It was higher in males and rural areas.Our data indicate that geographical exposures, gender, age, and factors correlated with rural residence impact HHV-8 seropositivity in sub-Saharan Africa.

Objective: To perform a quantitative estimate of the proportion of cancers attributable to occupational exposures in France in 2000. Methods: Exposure data for established carcinogens were obtained from a 1994 survey and other sources. Relative risks for 23 exposure-cancer combinations were derived from meta-analyses and pooled analyses. Results: A total of 4335 cases of cancer among men (2.7% of all cancers) and 403 cases among women (0.3% of all cancers) were attributed to occupational exposures. Asbestos, polycyclic aromatic hydrocarbons, and chromium VI were the main occupational carcinogens in men, and asbestos and involuntary smoking were the main carcinogens in women. Corresponding proportions for cancer deaths were 4.0% and 0.6% in men and women, respectively. Lung cancer represented 75% of deaths attributable to occupational exposures. Conclusion: Our estimates are comparable with those obtained for other countries in studies based on similar methodology. Copyright © 2010 by American College of Occupational and Environmental Medicine.

Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs inITGA9at 3p21.3 and 9 SNPs within the 6p21.3HLAregion were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC).Results.The reported associations betweenITGA9variants and NPC were not replicated. Multiple loci ofGABBR1,HLA-F,HLA-A, andHCG9were statistically significant in both cohorts (Pcombinedrange from 5.96 × 10−17to 0.02). We show for the first time that these factors influence NPC development independent of environmental risk factors. This study also indicated that the SNP alone cannot serve as a predictive/diagnostic marker for NPC. Integrating the most significant SNP with IgA antibodies status to EBV, which is presently used as screening/diagnostic marker for NPC in Chinese populations, did not improve the AUC estimate for diagnosis of NPC.

We assessed the immunogenicities and efficacies of two highly attenuated vaccinia virus-derived NYVAC vaccine candidates encoding the human T-cell leukemia/lymphoma virus type 1 (HTLV-1)envgene or both theenvandgaggenes in prime-boost pilot regimens in combination with naked DNA expressing the HTLV-1 envelope. Three inoculations of NYVAC HTLV-1envat 0, 1, and 3 months followed by a single inoculation of DNAenvat 9 months protected against intravenous challenge with HTLV-1-infected cells in one of three immunized squirrel monkeys. Furthermore, humoral and cell-mediated immune responses against HTLV-1 Env could be detected in this protected animal. However, priming the animal with a single dose ofenvDNA, followed by immunization with the NYVAC HTLV-1gagandenvvaccine at 6, 7, and 8 months, protected all three animals against challenge with HTLV-1-infected cells. With this protocol, antibodies against HTLV-1 Env and cell-mediated responses against Env and Gag could also be detected in the protected animals. Although the relative superiority of a DNA prime-NYVAC boost regimen over addition of the Gag component as an immunogen cannot be assessed directly, our findings nevertheless show that an HTLV-1 vaccine approach is feasible and deserves further study.

The aim of this study was to investigate the distribution of human T-cell leukemia virus type 1 (HTLV-1) in various organs of serially sacrificed squirrel monkeys (Saimiri sciureus) in order to localize the reservoir of the virus and to evaluate the relationship between viral expression and the humoral or cellular immune response during infection. Six squirrel monkeys infected with HTLV-1 were sacrificed 6, 12, and 35 days and 3, 6, and 26 months after inoculation, and 20 organs and tissues were collected from each animal. PCR and reverse transcription-PCR (RT-PCR) were performed with gag and tax primers. Proviral DNA was detected by PCR in peripheral blood mononuclear cells (PBMCs) of monkeys sacrificed 6 days after inoculation and in PBMCs, spleens, and lymph nodes of monkeys sacrificed 12 and 35 days and 3, 6, and 26 months after inoculation. Furthermore, tax/rex mRNA was detected by RT-PCR in the PBMCs of two monkeys 8 to 12 days after inoculation and in the spleens and lymph nodes of the monkey sacrificed on day 12. In this animal, scattered HTLV-1 tax/rex mRNA-positive lymphocytes were detected by in situ hybridization in frozen sections of the spleen, around the germinal centers and close to the arterial capillaries. Anti-HTLV-1 cell-mediated immunity was evaluated at various times after inoculation. Anti-p40 Tax and anti-Env cytolytic T-cell responses were detected 2 months after infection and remained detectable thereafter. When Tax peptides were used, this response appeared to be directed against various Tax epitopes. Our results indicate that squirrel monkeys represent a promising animal model for studying the early events of HTLV-1 infection and for evaluating candidate vaccines against HTLV-1. Human T-cell leukemia/lymphoma virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia (36) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/ HAM) (10), has also been associated with pediatric infectious dermatitis (22), uveitis (24), and some cases of arthropathy (13) and polymyositis (25). Owing to the inherent difficulty of obtaining human specimens in early HTLV-1 infection, a relevant animal model is essential for better understanding of the seeding of HTLV-1 in various organs. We showed recently that the squirrel monkey Saimiri sciureus, a South American nonhuman primate which is free of simian T-cell leukemia virus, is susceptible to experimental infection with syngeneic or allogeneic HTLV-1-immortalized cells (19). As in humans, such experimental inoculation leads to chronic infection, HTLV-1 provirus being detectable in peripheral blood mononuclear cells (PBMCs) by PCR up to 36 months after inoculation. Chronically infected monkeys, like HTLV-1-infected humans, develop high titers of antibodies against the structural proteins of the virus (19). In infections with human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), the lymph nodes are reservoirs that contain a large viral load during the asymptomatic stage (8, 29). A significant percentage of latently infected lymphocytes are found in the lymph nodes and constitute a target for later viral reactivation (7). Indeed, during clinical latency in HIV or SIV infection, productively infected cells are detected at higher frequency in lymph nodes than in peripheral blood, indicating the progressive involvement of the lymphoid organs in HIV infection (2, 21, 27). These findings show that HIV is widely disseminated in lymphoid tissue relatively early in infection. In contrast, little is known about the role of the lymphoid tissues in the early phases of HTLV-1 infection. The aim of the present study was to investigate the early events in HTLV-1 infection and specifically the distribution of the HTLV-1 provirus in various organs of serially sacrificed squirrel monkeys, to localize the reservoir of the latent virus, and to evaluate the humoral and cellular immune responses to infection.

Molecular subtyping was used to investigate the epidemiology of human T-lymphotropic virus type II (HTLV-II) in the United States. Nested polymerase chain reaction of the HTLV-II long terminal repeat region followed by restriction fragment length polymorphism (RFLP) analysis was performed on HTLV-II seropositive subjects including 97 U.S. blood donors without major risk factors for HTLV-II infection, 53 injection drug users (IDU), and 10 American Indian blood donors. Three new HTLV-II RFLP types were confirmed with DNA sequencing and phylogenetic analysis. HTLV-II RFLP type a0 (Switzer classification) was associated with older age [adjusted odds ratio (OR) 1.06 per year of age, 95% confidence interval (CI) 1.02±1.09] and with Black (OR 5.24, 95% CI 1.90±14.47) and White (OR 4.43, 95% CI 1.67±11.75) race/ ethnicity. These data are consistent with an age±cohort effect for HTLV-II RFLP type a0 among older White and Black IDU and blood donors. This finding could be explained by an epidemic of non-a0 HTLV-II RFLP types among younger persons of Hispanic and other race/ethnicity, superimposed upon endemic HTLV-II RFLP type a0 among older Black and White persons. © 1998 Academic Press

The interpretation of Western blot patterns according to differing seropositivity criteria represents a major obstacle to determining the seroprevalence of human T-cell lymphotropic virus (HTLV)-1 especially in tropical Africa and Melanesia where a high percentage of Western blots exhibit an indeterminate pattern. This study reviewed HTLV-1 seroprevalence in different ethnic groups and geographic areas of Cameroon by using stringent Western blot criteria and compared the epidemiologic determinants of HTLV-1 prevalence with those of HTLV-1-indeterminate patterns. HTLV-1 prevalence averaged 1.1% among 3783 rural residents of Cameroon. This rate was higher among females (1.5%) and Pygmies (2.0%) and increased with age. 1.6% of the population clustered in tropical forests of southern Cameroon demonstrated a unique HTLV-1 Gag-indeterminate Western blot profile showing strong reactivities to p19 p26 p28 p32 p36 and pr 53 but lacking p24 and env reactivity. Unlike HTLV-1 the seroprevalence of this pattern did not increase with age or differ by sex. Such a Western blot profile is considered to reflect a viral or parasitic factor endemic in tropical rain forest areas rather than an HTLV-1-related viral infection.

Peripheral blood mononuclear cells (PBMC) from three adult male squirrel monkeys ( Saimiri sciureus ) were transformed by human T-cell leukemia/lymphoma virus type I (HTLV-I) by cocultivation with lethally irradiated human MT-2 cells. Three permanent monkey T-cell lines producing HTLV-I were obtained and characterized. Six weeks after inoculation seroconversion was observed in three of three monkeys inoculated with autologous transformed T cells and in two of three monkeys receiving homologous cells. Proviral DNA was detected in their PBMC at various times after inoculation, with the highest proviral load and antibody titers being found in monkeys infected with homologous cells. Monkeys inoculated with heterologous MT-2 cells did not seroconvert, and HTLV-I provirus was detected only transiently in their PBMC. To determine whether in vitro and in vivo HTLV-I infection of squirrel monkey cells led to a selection of monkey-adapted viral mutants, comparative sequencing of the proviral gp21 env between ex vivo monkey HTLV-I-infected PBMC, the inoculum, and MT-2 cells was done and no significant differences were detected. The squirrel monkey, which is naturally free of simian T-cell leukemia/lymphoma virus, thus appears to be a suitable model for evaluating HTLV-I candidate vaccines and for studying the pathogenesis of HTLV-I.

Human T cell lymphotropic virus type II (HTLV-II) and its two genomic subtypes, A and B, which differ by 3 to 6% at the nucleotide level (depending on the gene studied), were until recently considered to be endemic only in certain Indian tribes in the Americas and were therefore considered mainly as a "New World virus." First, the evidence of HTLV-II antibodies and later characterization of isolates from sex workers or individuals living in large West and Central African cities suggested that HTLV-II subtype A could have been imported recently in Africa. However, the findings of HTLV-II infection in two Pygmy populations living in remote areas of Zaire and Cameroon suggest that HTLV-II might have been in Africa for a very long time. Furthermore, the discovery of HTLV-II subtype B virus in some of these Pygmies, but also in other individuals from Zaire and within a family in Gabon for three generations, confirms the hypothesis of a very ancient presence of this HTLV-II subtype B on the African continent Recent data indicate also that there exist in Central Africa specific HTLV-II divergent strains including an HTLV-II B variant strain in Gabon. In the context of recent evidence for interspecies transmission in Central and West Africa of HTLV-I/simian T cell lymphotropic virus type I (STLV-I) strains, leading to the two major HTLV-I African subtypes, we would like to suggest that some STLV-II (closely related to HTLV-II subtype B) still exist or might have existed in Central/East Africa. The recent finding of quite divergent primate T cell lymphotropic viruses (PTLVs) in several Pygmy chimpanzees of Zairian origin (PTLV-PP1664 and STLV-PP) and in wild-caught baboons in Eritrea, Ethiopia (PTLV-L), also supports the complementary hypothesis of a yet to be discovered new HTLV-II-related virus in humans. Careful study of the indeterminate Western blot patterns present in some populations in Central Africa strongly suggests that such an exciting possibility exists, thus opening new avenues of research on both the history of primate retroviruses and that of early human groups.

Among 332 female sex workers in Douala, Cameroon, 113 were HIV-1 seropositive, 3 were HTLV-I seropositive, and only 1 had specific anti-HTLV-II antibodies. By cocultivation with BJAB cells, an HTLV-II was isolated from the peripheral blood mononuclear cells of this 32-year-old woman coinfected by HIV-1. This new African HTLV-II isolate (PH230PCAM) belongs to the molecular subtype A, exhibiting, however, a nucleotide variability of 2.4% and 0.8%, vis-à-vis the MO prototype, in the LTR and in the gp21 env gene, respectively. These data, as well as the previous findings of another HTLV-II subtype A in a Ghanean prostitute, suggest that this viral subtype had been imported into Africa, while the HTLV-II subtype B, described in remote areas of Zaire, Gabon, and Cameroon, could be a genuine African HTLV-II, present in this continent for a long period of time.

An epidemiological study was performed in French Guiana (population 115,000) to determine the prevalence and incidence of adult T-cell leukemia/lymphoma (ATL) associated with human T-cell leukemia/lymphoma virus type I (HTLV-I). From January 1990 to December 1993, all suspected cases of ATL were enrolled in this study, and their clinical, epidemiological and immunovirological features were analyzed. Out of the 19 suspected cases, 18 were considered as ATL associated with HTLV-I (8 acute forms, 8 lymphoma types and 2 smoldering cases). Before this study, only 2 ATL cases had been reported in French Guiana over a 10-year period. This demonstrates that the number of ATL cases is greatly underestimated in most tropical HTLV-I endemic areas unless a specific disease search is performed. The mean age of the patients was 41 years. While HTLV-I antibodies were present in all cases, molecular studies demonstrated a clonal integration of HTLV-I in the tumoral cells in 7 cases out of the 9 tested. Fifteen patients died within a year of diagnosis. The crude incidence rate of ATL in French Guiana is around 3.5/100,000/year, a situation similar to that found in the Caribbean and in HTLV-I-endemic regions of Japan. However it reaches around 30/100,000/year (highest incidence ever described) in a small remote ethnic group of African origin (around 6200 inhabitants). Possible causes of ATL clustering in this ethnic group are presented. © 1995 Wiley-Liss, Inc.

The frequency of indeterminate Western blot (WB) seroreactivities against HTLV-I “gag encoded proteins” only, and the use of low specific diagnostic WB criteria led to the overestimation of HTLV-I seroprevalence in initial studies in intertropical Africa and Papua New Guinea. In order to clarify the meaning of such seroreactivity, 98 blood samples of individuals from a high HTLV-I endemic area in Zaire, Central Africa were studied by a WB assay containing HTLV-I disrupted virions enriched with a gp 21 recombinant protein and a synthetic peptide from the gp 46 region (MTA-1), and by the polymerase chain reaction (PCR) with 3 primers pairs and 4 different HTLV-I and or HTLV-II-specific probes. These 98 samples were taken mainly from patients with neurological diseases and from their relatives. Using stringent WB criteria, 28 sera (29%) were considered as HTLV-I-positive, 3 as negative and 67 (68%) as indeterminate. A large proportion of these indeterminate sera would have been considered as HTLV-I-positive samples according to previous low specific WB diagnostic criteria. After PCR, 35 samples (36%) were considered as positive for the presence of HTLV-I proviral DNA. Out of the 67 WB seroindeterminate, 10 (15%) were found HTLV-I-positive by PCR. These 10 individuals exhibited in WB multiple band reactivity with p19 and/or p24 (7 cases of both) associated in 6 cases with rgp 21, but never with MTA-1. No samples were found PCR-positive for HTLV-II despite the findings of 11 sera suggestive of HTLV-II by WB. These findings demonstrate that even in a high HTLV-I endemic area, only a minority (about 15%) of the WB-seroinde-terminate individuals could be considered as infected by HTLV-I, and that very stringent WB criteria could lead to overlooking some infected individuals. © 1994 Wiley-Liss, Inc.

The susceptibilities of different strains of inbred rats to infection with the human T-cell leukemia virus (HTLV-I) after inoculation of human HTLV-I producer cell lines were compared. The Fisher F344 and Brown Norway strains developed the highest antibody response to HTLV-I, while the Lewis and BB strains were low responders. Antibodies against the HTLV-I gag proteins, and env gp21 but not env gp46, were detected in Western blots with sera from HTLV-I-infected Fischer F344 and Brown Norway rats. These sera were inactive in an in vitro syncytium-formation inhibition test. The HTLV-I provirus was detected by polymerase chain reaction in all Fischer F344, and some Lewis and Brown Norway rats, but not in the BB, which lack CD8+ T lymphocytes. The most frequent locations of the HTLV-I provirus in the Fischer F344, Lewis and Brown Norway rats at 12 weeks after infection were the peripheral blood mononuclear cells (PBMC) and spinal cord. In a second experiment in Brown Norway rats, the provirus was again detected in the PBMC of rats at 12 weeks, but not at 22 weeks, and among the other organs tested at 22 weeks the sympathetic nerve ganglia were positive. It is concluded that HTLV-I infection occurs in adult rats, but is suppressed with time.

International audience; Background. The presence and origin of endemic foci of human T-lymphotropic virus type 2 (HTLV2) infection in Africa remain a matter of debate. Methods. To better appreciate such determinants, we performed a survey of 1918 inhabitants from Cameroon forest areas, including 1051 Bakola Pygmies and 867 Bantus. Results. The overall HTLV-1/2 seroprevalence was 4% (49 cases of HTLV-1 and 27 cases of HTLV-2 infection). Both infections were mainly restricted to the Bakola Pygmies, with surprisingly no HTLV-2 infections in the Bantu population. Both HTLV-1 and HTLV-2 seroprevalences increased with age. There was evidence of ongoing HTLV-2 transmission in this population. Lymphoid T cell lines producing HTLV-2 were established. HTLV-2 long terminal repeat sequences (672 base pairs) obtained from 7 infected Bakola were highly similar to each other (

A squirrel monkey model of human T-cell leukemia virus type 1 (HTLV-1) infection was used to evaluate the immunogenicity and protective efficacy of a chimeric peptide vaccine composed of a B-cell epitope from the envelope region (aa 175–218) and three HLA-A*0201-restricted cytotoxic T-lymphocyte epitopes derived from Tax protein (Tri-Tax). These selected Tax peptides induced secretion of gamma interferon (IFN-γ) in peripheral blood mononuclear cells obtained from monkeys chronically infected with HTLV-1. After immunization, a high titre of antibodies and a high frequency of IFN-γ-producing cells were detected against the Env and the Tri-Tax immunogens, but not against the individual Tax peptides. This might indicate that epitope(s) distinct from those recognized by humans are recognized by responder monkeys. After challenge, it was shown by competitive PCR that partial protection against HTLV-1 infection could be raised in immunized animals. Further studies should be developed to determine the duration of this protection.

The Inter-Academy Panel (IAP) is critical about the scarce support to mother-child health (MCH) research in developing countries. At the request of the IAP, a group of members of the French and Swedish Academies of Science have arrived at the conclusion that an efficient network between scientists in resource-poor and industrialized countries will facilitate MCH research in developing countries. The priorities for such a network have been listed as follows: The present organization for the MCH website at the Pasteur Institute in Paris should be adapted to better promote collaboration between scientists from industrialized and developing countries. To provide short-term courses for young scientists from developing countries in the design of research protocols, and in the writing of scientific reports and manuscripts. To organize workshops on various topics of relevance for MCH in developing countries in order to create new research networks for scientific collaboration between industrialized and resource-poor countries. To establish collaboration between non-governmental organizations (NGOs) that support MCH research in developing countries. Topics for such collaborative studies and the way in which they may be performed are summarized.

International audience; Kaposi's-sarcoma-associated herpesvirus(KSHV)/human-herpes-virus-8(HHV-8) sequences originally detected in AIDS-associated Kaposi's sarcoma have been found in almost every KS tested, whether endemic, classic, iatrogenic or epidemic. Most of the studies on African KS involved East African patients. We report herewith the study of 17 African or Guyanan KS patients, 3 with epidemic KS (EKS) from Central African Republic, 3 from Senegal (2 EKS and 1 endemic KS), 3 EKS from Cameroon and 8 from French Guiana (3 EKS and 5 endemic KS). Serum-specific antibodies directed against latent and/or lytic HHV-8 antigens were present in 16 of them (94%), detected either by immunofluorescence assay and/or by immunoperoxidase. Polymerase chain reaction (PCR), using specific primers for HHV-8 ORF26 (233 bp) and ORF75 (601 bp), was carried out on DNA extracted from KS cutaneous biopsies, clinically uninvolved skin biopsies and peripheral-blood mononuclear cells (PBMC). HHV-8 DNA was detected in 16 out of 16 (100%) KS biopsies, regardless of their origin or clinico-pathological sub-type, in 7 out of 15 (47%) normal skin samples and 7 out of 16 (44%) PBMC. Comparative PCR, carried out in 7 patients, regularly found a much higher viral load in KS biopsies than in autologous normal skin and PBMC samples. Sequencing of fragments of the ORF26 and of the ORF75 demonstrated that the 16 HHV-8 strains were of the A, B or C sub-type. Furthermore, sequences of the entire ORF K1 of 4 strains showed that these HHV-8 strains of African origin were of the A5 or the B sub-type.

The Epstein Barr virus (EBV) is an ubiquitious human Herpes Virus. It causes infectious mononucleosis and is closely associated with two neoplasms: Burkitt’s lymphoma (BL) and nasopharyngeal carcinoma (NPC) (1). In NPC epithelial cells the viral genome has been detected in both tumor biopsies by hybridization techniques and in tumors transplanted in nude mice (which are free of infiltrating B lymphocytes). EBV can latently infect its target cells, but different observations favor the hypothesis that viral replication occurs in the tumor: analysis of the structure of viral DNA termini has demonstrated the presence of linear viral DNA, specifically indicating that the viral productive cycle may occur in these tumors (2); in NPC tumor biopsies different RNAs from the replicative phase of the EBV life cycle have been detected. In NPC patients, elevated IgG and IgA antibodies directed against EA and VCA viral proteins EBV reactivation occur in those subjects. It appears then that the EB virus can be partially in the productive phase of its cycle. The molecular mechanism leading to EBV activation is begining to be understood and transactivators encoded by the EBV genome have been identified and have been shown to be involed in the activation of the lytic cycle(3,4,5,6,7,8).

Three aspects of the rat model of HTLV-I/II infection were investigated. (i) The efficacy of HTLV-I-transformed rat cell lines in infecting different strains of rats: WKY and Lewis HTLV-I-transformed cell lines were injected into adult WKY, Lewis and Brown Norway rats, representing syngeneic and allogeneic combinations. The HTLV-I provirus was not detected in peripheral-blood mononuclear cells (PBMC) from these rats 18 weeks after inoculation, showing that HTLV-I-transformed rat cells are not suitable for virus challenge in vaccination experiments. Rats inoculated with Lewis HTLV-I-transformed cells produced an antibody response to HTLV-I, which was higher in allogeneic (WKY and Brown Norway) than in syngeneic rats. (ii) The susceptibility of rats to HTLV-II infection: After human HTLV-II-producing cells (MO) were injected into adult WKY rats, the HTLV-II provirus was detected in PBMC 12 weeks later. Sequencing of a portion of this provirus confirmed its identity with the HTLV-II from MO cells. (iii) The role of MHC haplotype in susceptibility to neurological disease in rats inoculated as newborns with HTLV-I: The hypothesis that the RT-Ik haplotype confers susceptibility was tested by inoculating newborn OKA (RT-Ik), WKY (RT-Il), Lewis (RT-Il) and Fischer 344 (RT-I lvl) rats with human HTLV-I-producing cells (MT-2). Eighteen months later, only the WKY rats showed histological abnormality of the spinal cord, without clinical paralysis. Fischer 344 rats developed cutaneous tumors and OKA rats mammary tumors. The HTLV-I provirus was not detected in these tumors.