Human Oncogenic Viruses: Characteristics and Prevention Strategies-Lessons Learned from Human Papillomaviruses.

Approximately 12% of human cancers worldwide are associated with infectious agents, which are classified by the International Agency for Research on Cancer (IARC) as Group 1 within the agents that are carcinogenic to humans. Most of these agents are viruses. Group 1 oncogenic viruses include hepatitis C virus, hepatitis B virus (HBV), human T-cell lymphotropic virus type 1, Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, human immunodeficiency virus-1 and high-risk human papillomaviruses (HPVs). In addition, some human polyomaviruses are suspected of inducing cancer prevalently in hosts with impaired immune responses. Merkel cell polyomavirus has been associated with Merkel cell carcinoma and included by the IARC in Group 2A (i.e., probably carcinogenic to humans). Linking viruses to human cancers has allowed for the development of diagnostic, prophylactic and therapeutic measures. Vaccination significantly reduced tumours induced by two oncogenic viruses as follows: HBV and HPV. Herein, we focus on mucosal alpha HPVs, which are responsible for the highest number of cancer cases due to tumour viruses and against which effective prevention strategies have been developed to reduce the global burden of HPV-related cancers.

Milk Transmission of Mammalian Retroviruses.

The transmission of viruses from one host to another typically occurs through horizontal or vertical pathways. The horizontal pathways include transmission amongst individuals, usually through bodily fluids or excretions, while vertical transmission transpires from mother to their offspring, either during pregnancy, childbirth, or breastfeeding. While there are more than 200 human pathogenic viruses to date, only a small number of them are known to be transmitted via breast milk, including cytomegalovirus (CMV), human immunodeficiency virus type 1 (HIV-1), and human T cell lymphotropic virus type 1 (HTLV-1), the latter two belonging to the family Retroviridae. Breast milk transmission is a common characteristic among mammalian retroviruses, but there is a lack of reports summarizing our knowledge regarding this route of transmission of mammalian retroviruses. Here, we provide an overview of the transmission of mammalian exogenous retroviruses with a focus on Orthoretrovirinae, and we highlight whether they have been described or suspected to be transmitted through breast milk, covering various species. We also elaborate on the production and composition of breast milk and discuss potential entry sites of exogenous mammalian retroviruses during oral transmission.

Gene expression and TCR amino acid sequences selected by HLA-A02:01-restricted CTLs specific to HTLV-1 in ATL patients.

Adult T-cell leukaemia/lymphoma (ATL) is an aggressive malignancy of peripheral T cells caused by human T-cell lymphotropic virus type-1 (HTLV-1). Tax is the most important regulatory protein for HTLV-1. We aimed to reveal a unique amino acid sequence (AA) of complementarity-determining region 3 (CDR3) of the T-cell receptor (TCR)ß and TCRα chains of HLA-A*02:01-restricted Tax11-19 -specific cytotoxic T cells (Tax-CTLs). The gene expression profiles (GEP) of Tax-CTLs were assessed by the next-generation sequence (NGS) method with SMARTer technology. Tax-CTLs seemed to be oligoclonal, and their gene compositions were skewed. The unique motifs of 'DSWGK' in TCRα and 'LAG' in TCRß at CDR3 were observed in almost all patients. Tax-CTL clones harbouring the 'LAG' motif with BV28 had a higher binding score than those without either of them, besides a higher binding score associated with longer survival. Tax-CTLs established from a single cell showed killing activities against Tax-peptide-pulsed HLA-A2+ T2 cell lines. GEP of Tax-CTLs revealed that genes associated with immune response activity were well preserved in long-term survivors with stable status. These methods and results can help us better understand immunity against ATL, and should contribute to future studies on the clinical application of adoptive T-cell therapies.

Cognitive deficits in HTLV-1 patients.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus known to be associated with adult T-cell lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Previous researches and brain imaging techniques have suggested cognitive abnormalities as well as brain damage in individuals infected with this virus. Given the insufficient amount of studies on how this virus can impact the affected person's cognition, we aimed to assess and compare the cognitive abnormalities of HAM/TSP patients, asymptomatic HTLV-1 carriers, and healthy controls. This cross-sectional study was conducted on 51 patients divided into 3 groups; a group of HAM/TSP patients, a group of asymptomatic HTLV-1 carriers, and an uninfected control group. Each group contained 17 members. The cognitive state of the studied population was assessed using the Mini-Mental State Exam (MMSE), Symbol Digit Modalities Test (SDMT), Rey-Osterrieth complex figure test (ROCF), the "Verbal Fluency Test" and the "Trail Making Test" (TMT) components of the Delis-Kaplan executive function system (D-KEFS) test, the Rey Auditory Verbal Learning Test (RAVLT), and digit span memory test. Patients diagnosed with HAM/TSP received significantly lower scores on the SDMT, ROCF, TMT, RAVLT, digit span memory test, and the orientation, calculation, and recall component of the MMSE assessment (p-value < 0.001). In addition, the asymptomatic HTLV-1 carriers obtained lower scores on the SDMT, ROCF, digit span memory test, and the orientation, calculation, and recall component of the MMSE assessment compared to the control group (p-value < 0.001). Overall, the findings suggest that HAM/TSP, or an asymptomatic infection with HTLV-1 could lead to cognitive deficits in the affected individuals. This can further emphasize the importance of assessing the cognitive function and psychiatric abnormalities of those infected with this virus.

CAR-iNKT cells targeting clonal TCRVß chains as a precise strategy to treat T cell lymphoma.

Introduction: Most T cell receptor (TCR)Vß chain-expressing T cell lymphomas (TCL) including those caused by Human T cell leukaemia virus type-1 (HTLV-1) have poor prognosis. We hypothesised that chimeric antigen receptor (CAR)-mediated targeting of the clonal, lymphoma-associated TCRß chains would comprise an effective cell therapy for TCL that would minimally impact the physiological TCR repertoire. Methods: As proof of concept, we generated CAR constructs to target four TCRVß subunits. Efficacy of the CAR constructs was tested using conventional T cells as effectors (CAR-T). Since invariant NKT (iNKT) cell do not incite acute graft-versus-host disease and are suitable for 'off-the-shelf' immunotherapy, we generated anti-TCRVß CAR-iNKT cells. Results: We show that anti-TCRVß CAR-T cells selectively kill their cognate tumour targets while leaving >90% of the physiological TCR repertoire intact. CAR-iNKT cells inhibited the growth of TCL in vivo, and were also selectively active against malignant cells from Adult T cell leukaemia/lymphoma patients without activating expression of HTLV-1. Discussion: Thus we provide proof-of-concept for effective and selective anti-TCRVß CAR-T and -iNKT cell-based therapy of TCL with the latter providing the option for 'off-the-shelf' immunotherapy.

HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England.

OBJECTIVES: HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1/HTLV-2 seroprevalence amongst HIV-PrEP users in England. METHODS: An unlinked anonymous seroprevalence study. RESULTS: Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1/HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). CONCLUSIONS: There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.

Clinical Features and Possible Origin of Preretinal Deposits in Different Ocular Diseases and Events: A Narrative Review.

Preretinal deposits (PDs) are a rare condition among fundus diseases. We found that preretinal deposits have some features in common that can provide clinical information. This review affords an overview of PDs in different but related ocular diseases and events, and summarizes the clinical features and possible origin of PDs in related conditions, providing diagnostic clues for ophthalmologists when facing PDs. A literature search was performed using three major electronic databases (PubMed, EMBASE, and Google Scholar) to identify potentially relevant articles published on or before June 4, 2022. Most of the cases in the enrolled articles had optical coherence tomography (OCT) images to confirm the preretinal location of the deposits. Thirty-two publications reported PD-related conditions, including ocular toxoplasmosis (OT), syphilitic uveitis, vitreoretinal lymphoma, human T-cell lymphotropic virus type 1 (HTLV-I) associated uveitis or HTLV-I carriers, acute retinal necrosis, endogenous fungal endophthalmitis, idiopathic uveitis, and exogenous materials. Based on our review, OT is the most frequent infectious disease to exhibit PDs, and silicone oil tamponade is the most common exogenous cause of preretinal deposits. PDs in inflammatory diseases are highly suggestive of active infectious disease and are preferentially accompanied by a retinitis area. However, PDs will largely resolve after etiological treatment in either inflammatory or exogenous conditions.

Panuveitis induced by donor-derived CD8+ T cells after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia.

Purpose: This article presents a case of panuveitis that occurred after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a patient with lymphoma-type human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL). Observations: A 45-year-old man developed unilateral panuveitis 18 months after undergoing allo-HSCT. He underwent vitrectomy, and depositions of grey-white granules localized on the retinal artery were observed in the eye. Cytological examination of the vitreous aspirates showed that the atypical lymphoid cells stained positive for CD3 and CD8, but negative for CD4, B-cell markers, and cytomegalovirus antigen. Interphase fluorescence in situ hybridization using X- and Y-chromosome probes revealed complete donor chimerism in CD8+ T cells in the vitreous aspirates. Conclusions and importance: Donor-derived CD8+ T lymphocytes can induce panuveitis like HTLV-1-assiciated uveitis after allo-HSCT in patients with ATL. Pathological diagnosis of vitreous infiltration by vitrectomy is helpful in patients with ATL. Donor-derived CD8+ T lymphocytes-induced panuveitis is recurrent but susceptible to regional corticosteroid treatment.

HTLV-1 Tax-specific memory cytotoxic T lymphocytes in long-term survivors of aggressive-type adult T-cell leukemia/lymphoma.

PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is a relatively refractory peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type 1 (HTLV-1). The objective of this study was to investigate the characteristics of long-term survivors with ATLL. METHODS: We conducted an observational study of 75 aggressive-type ATLL patients. Flow cytometry was conducted to analyze HTLV-1 Tax-specific cytotoxic T-lymphocytes (CTLs) and T-cell receptor Vß gene repertoire. RESULTS: We first evaluated six long-term survivors among 37 patients who were newly diagnosed with ATLL and then treated with intensive chemotherapy without mogamulizumab, a monoclonal antibody for C-C chemokine receptor four antigen. Reversal of the CD4-to-CD8 ratio (CD4/CD8) in peripheral mononuclear cells was observed in all six patients. Three of these six patients showed reversed CD4/CD8 immediately after herpes virus infection. Four of these six patients who could be examined demonstrated long-term maintenance of HTLV-1 Tax-specific CTLs. We subsequently identified four long-term survivors among 38 patients who were newly diagnosed with ATLL and then treated with intensive chemotherapy plus mogamulizumab. All four patients showed reversed CD4/CD8, and three of the four patients contracted herpes virus infection during immunochemotherapy. Six of the total 10 patients were subjected to CTL analyses. Tax-specific CTLs were observed, and the CTLs that were almost entirely composed of memory CTLs in all patients were recorded. HTLV-1 provirus was also detected in all six patients. CONCLUSIONS: These data suggest that Tax-specific memory CTLs probably, together with anticancer agents, eradicate ATLL cells and exhibit long-term preventive effects from relapse ATLL. Thus, the strong activation of cellular immunity, such as herpes virus infection, seems to be necessary to induce such a potent number of Tax-specific CTLs.

COVID-19 in a human T-cell lymphotropic virus type-1 carrier.

This is the first report of COVID-19 in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. HTLV-1 infection can cause immune dysfunction even in asymptomatic carriers. This case highlights the need for guidance on management of COVID-19-HTLV-1 coinfection, specifically on the appropriate use of corticosteroid treatment while considering secondary infection.

Impact of Human T Cell Lymphotropic Virus Type 1 and 2 Infection on Survival Following Stem Cell Transplantation.

Human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) are delta retroviruses. HTLV-1 may lead to complications, including adult T cell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy. Immunosuppression may result in progression from an asymptomatic carrier state to ATLL. Data on the safety of stem cell transplantation (SCT) in patients with HTLV-1/2 infection are lacking. The Center for International Blood and Marrow Transplant Research database was queried for patients who tested positive for HTLV infection in the pretransplantation workup and underwent either autologous SCT (autoSCT) or allogeneic SCT (alloSCT). Patients were excluded if they underwent SCT for ATLL. The primary outcome was overall survival (OS) at 3 years and 4 years post-SCT. In those who underwent autoSCT, 54 patients were HTLV-positive and 9836 were HTLV-negative. In those who underwent alloSCT, 105 patients were HTLV-positive and 18,077 were HTLV-negative. No difference in OS was noted between the HTLV-positive and HTLV-negative patients at 3 years post-autoSCT (76% versus 77%; P = .916). Inferior OS (32% versus 46%; P = .017) and nonrelapse mortality (35% versus 27%; P = .030) were observed in HTLV-positive patients at 4 years post-alloSCT. Future work should examine the mechanism by which HTLV-1/2 impact survival in alloSCT recipients.

Sjögren's Syndrome and Viral Infections.

Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This leads to dryness of the main mucosal surfaces such as the mouth, eyes, nose, larynx, pharynx, and vagina. Although there is little morbidity data at the initial diagnosis, SS may be a serious disease, with extra mortality caused by hematological cancer. The cause of SS is unknown, but factors postulated to play a role include genetic and environmental factors, hormonal abnormality, and viral infection. Under the influence of these factors, the immune system becomes abnormal and the tissue is damaged. In this study, we summarize recent developments in our understanding of the relationship between SS and viral infections, including Epstein-Barr virus (EBV), hepatitis C virus (HCV), human T cell lymphotropic virus type 1 (HTLV-1), cytomegalovirus (CMV), and human immunodeficiency virus (HIV).

The association of polymorphisms (rs2227981 and rs10204525) of PDCD1 gene with susceptibility to human T-cell leukemia virus type 1.

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus as the causative agent of two serious diseases in human is known. Programmed cell death-1 (PD-1) is a regulatory protein that has an important role in immune system response and created exhaustion phenotype in T cells at chronic infections; therefore, it can impair anti-viral responses. Since the single nucleotide polymorphisms (SNP) in PD-1gene may influence infection with HTLV-1virus, so in this research, association between SNPs in exon 5 of PD-1 gene with susceptibility to HTLV-1 infection and proviral load (PVL) in Iran's population studied. In this case-control study, PD-1 rs2227981 and rs10204525 polymorphisms were evaluated in 81 HTLV-1 asymptomatic carriers (ACs) and 162 healthy individuals (control groups). These polymorphisms were genotyped by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, PVL was detected by quantitative real-time PCR (Q-RT-PCR). The results indicated that frequency of GA and AA genotypes in rs10204525 polymorphism was higher in ACs group (82.7%) than control group (26.5%) significantly; and GA + AA genotypes were significantly associated with HTLV-1 infection (OR = 13.244, 95%CI = 6.755-25.968, p = 0.000); but CT + TT genotypes in rs2227981 polymorphism, were as a protective factor against HTLV-1 infection (OR = 0.473, 95%CI = 0.279-0.813, P = 0.009). However, there was no significant difference between these polymorphisms and HTLV-1 PVL.

Uso da eletromiografia de superfície na resultância do treinamento muscular inspiratório com carga linear em portadores do vírus linfotrópico humano tipo 1 / Use of surface electromyography in results of inspiratory muscle training with linear load in patients with type 1 human lymphotropic virus

Este estudo visa avaliar por eletromiografia de superfície o comportamento dos músculos inspiratórios no treinamento muscular em voluntários com vírus linfotrópico de célula T humana do tipo 1. Trata-se de um ensaio clínico. Sete voluntários, com idade 58,85 ± 7,2) anos, realizaram treinamento muscular inspiratório domiciliar por 4 semanas, 3 vezes por semana, 30 minutos diários por meio de incentivador de carga linear. Para avaliação utilizou-se os dados de pressão inspiratória máxima e os dados da eletromiografia de superfície nas fases pré (T0), segunda semana (T2) e após a quarta semana (T4) de treinamento. Observou-se aumento progressivo da força muscular inspiratória de T0 a T4 (p = 0,007), assim como, aumento do recrutamento das unidades motoras pela análise da amplitude do sinal eletromiográfico, sendo mais evidente para o músculo esternocleidomastóideo (p = 0,12) em comparação ao músculo diafragma (p = 0,6). Verificou-se que no decurso do treinamento muscular ocorreu melhora significativa da força muscular inspiratória com maior recrutamento das fibras musculares dos músculos analisados na amostra. (AU)

This study aimed to evaluate by surface electromyography the behavior of inspiratory muscles in the muscle training of volunteers with human T-cell lymphotropic virus type 1. This was a clinical trial. Seven volunteers, 58,85 ± 7.21 years old, underwent inspiratory muscle training at home for 4 weeks, 3 times a week, 30 minutes daily by means of a linear load stimulator. The maximum inspiratory pressure data and the surface electromyography data were used for evaluation in the pre (T0), second week (T2) and after the fourth week (T4) training phases. There was a progressive increase in inspiratory muscle strength from T0 to T4 (p = 0.007), as well as an increase in the recruitment of motor units by analyzing the amplitude of the electromyographic signal, being more evident for the sternocleidomastoid muscle (p = 0.12) in comparison to the diaphragm muscle (p = 0.6). During the muscle training inspiratory muscle strength improves with greater recruitment of muscle fibers from the muscles analyzed in the sample. (AU)

Status of humoral and cellular immune markers in human T-cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers in northeastern Iran, Mashhad.

It is estimated that about 10-20 million peoples are infected with human T-cell leukemia virus type 1 (HTLV-1) around the world and suffered from HTLV-related diseases. The present study was aimed to evaluate the cellular immunity, T-cell activation, humoral immunity, and inflammatory response hallmarks which affect HTLV-1-associated disease progression. A total of 78 participants were included in the study, comprising 39 HTLV-1 asymptomatic careers (ACs) and 39 healthy controls. The HTLV-proviral load (PVL) was determined via real-time PCR technique, and anti-HTLV antibody, sIL2R, sCD30, Neoptrin, hs-CRP, IgE, anti-VCA, anti-EBNA, and anti-EA were assessed by ELISA method. Mean PVL in ACs was 352.7 ± 418.7 copies/104 PBMCs. A significant higher level of sIL-2R was observed in ACs (P < 0.0001). Anti-VCA antibody titer in ACs and healthy controls was 80.72 ± 105.95 and 156.05 ± 130.71, respectively (P = 0.007). Intriguingly, suppression in ACs immune response was not observed. Resultantly, HTLV-1 infection has no effect on the humoral immune response in ACs but greater T-cell activation and function cellular responses were detected. Finally, more studies on various immune markers in adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients are greatly needed to illuminate the association of ACs' immune status with the development of the related diseases.

Development of a Unique T Cell Receptor Gene-Transferred Tax-Redirected T Cell Immunotherapy for Adult T Cell Leukemia.

Adult T cell leukemia/lymphoma (ATL) is an aggressive peripheral T cell neoplasm caused by infection with human T cell lymphotropic virus type-1 (HTLV-1). Its prognosis remains extremely poor. Tax, the most important regulatory protein for HTLV-1, is associated with the aggressive proliferation of host cells and is also a major target antigen for CD8+ cytotoxic T cells (CTLs). Based on our previous findings that Tax-specific CTLs with a T cell receptor (TCR) containing a unique amino-acid sequence motif exhibit strong HLA-A*24:02-restricted, Tax301-309-specific activity against HTLV-1, we aimed to develop a Tax-redirected T cell immunotherapy for ATL. TCR-ɑ/ß genes were cloned from a previously established CTL clone and transduced into peripheral blood mononuclear cells (PBMCs) of healthy volunteers using a retroviral siTCR vector. Then the cytotoxic efficacy against HTLV-1-infected T cells or primary ATL cells was assessed both in vitro and in vivo. The redirected CTLs (Tax-siCTLs) produced a large amount of cytokines and showed strong killing activity against ATL/HTLV-1-infected T cells in vitro, although they did not have universal activity against ATL cells. Next, in a xenograft mouse model using an HTLV-1-infected T cell line (MT-2), in all mice treated with Tax-siCTLs, the tumor rapidly diminished and finally disappeared without normal tissue damage, although all mice that were untreated or treated with non-gene-modified PBMCs died because of tumor progression. Our findings confirm that Tax-siCTLs can exert strong anti-ATL/HTLV-1 effects without a significant reaction against normal cells and have the potential to be a novel immunotherapy for ATL patients.

The IL-18, IL-12, and IFN-γ expression in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, HTLV-1 carriers, and healthy subjects.

Interleukin (IL)-12, IL-18, and interferon gamma (IFN-γ) can induce Th1-inflammatory responses in favor of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) manifestation. In this study, the gene expression and plasma levels of these cytokines were evaluated. The peripheral blood mononuclear cells (PBMCs) in 20 HAM/TSP patients, 21 asymptomatic carriers (ACs), and 21 healthy subjects (HSs) were assessed for the expression of IL-18, IL-12, and IFN-γ, using qRT-PCR. The plasma level of IL-18 and IFN-γ were measured by an ELISA method. The mean of HTLV-1 proviral load (PVL) in the HAM/TSPs was 1846.59 ± 273.25 and higher than ACs at 719.58 ± 150.72 (p = 0.001). The IL-12 was considerably expressed only in nine ACs, five HAM/TSPs, and all HSs. Furthermore, the gene expression and plasma levels of IL-18 were lower in the HTLV-1-positive group than the control group (p = 0.001 and 0.012, respectively); however, there was no significant difference between the ACs and HAM/TSPs. The IFN-γ level was higher in the HTLV-1-positive group (p < 0.001) than HSs. Although there were no correlation between plasma levels of IL-18 and IFN-γ with PVL in the ACs, a positive correlation was observed between plasma IL-18 levels and PVL (r = 0.654, p = 0.002). The highest levels of IFN-γ were observed in the HAM/TSPs which has a significant correlation with HTLV-1-HBZ (r = 0.387, p = 0.05) but not with Tax. However, no significant correlation was found between PVL and proinflammatory pattern. Apart from the IFN-γ as a lymphokine, as a host factor, and HTLV-1-HBZ, as a viral agent, the other proinflammatory monokines or HTLV-1 factors are among the less-effective agents in the maintenance of HAM/TSP.

Organizing pneumonia in a carrier of human T-cell lymphotropic virus type-1.

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorders (HABAs) are pulmonary disorders with various interstitial lung disease patterns that often occur in HTLV-1 carriers. Among HABAs, organizing pneumonia (OP) is extremely rare. We present a case of an 82-year-old woman with OP as a HABA. This patient responded to corticosteroid therapy; however, the patient required the continuation of oral corticosteroid therapy to avoid OP relapse. In cases of OP as a HABA that are not stabilized by treatment with corticosteroids, continuation of oral corticosteroid therapy might be considered.

HTLV-1 Associated Neurological Complex. What is Hidden below the Water?

The human T-cell lymphotropic virus type 1 (HTLV-1) infects 5-10 million people worldwide and causes fatal and disabling diseases in a significant proportion of them. A chronic myelitis named HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the typical neurological manifestation of HTLV-1. However, other neurological syndromes can be either associated with HAM/TSP or occur in isolation in the HTLV-1 infected individual. Although this fact has been widely described over the years, it has been somewhat neglected by the mainstream literature, which has been largely focused on HAM/TSP. Cognitive dysfunction, encephalopathy, neurogenic bladder, motor neuron disease, inflammatory myopathies, polyneuropathy, and dysautonomia can also occur in the HTLV-1 infected patient and may remain unnoticed to the unsuspecting physician. In the present review, we intend to draw attention, primarily to the infectious disease specialist and to the general practitioner, to the fact that HTLV-1 has a broader neurological spectrum than the designation HAM/TSP suggests and that infected individuals may harbor other neurological syndromes in addition to HAM/TSP.

Virus-associated human cancers in Moroccan population: From epidemiology to prospective research.

Eight human viruses have been classified by the International Agency for Research on Cancer as carcinogenic or probably carcinogenic for humans. Infection with high risk human papillomaviruses, hepatitis B and C viruses, Epstein-Barr virus (EBV), human T-Cell Lymphotropic Virus Type 1 (HTLV-1), Human herpesvirus 8 (HHV-8), Merkel cell polyomavirus and human immunodeficiency virus-1 (HIV1) alone or in combination with other agents are the main etiologic factors of many cancers. This review highlights some aspects of virus-associated human cancers, potentially responsible for >14,000 malignancies per year in Morocco. Given that not all individuals infected with these viruses develop cancer, somatic alterations, genetic predisposition, and lifestyle or environmental factors obviously play potentializing roles modulating viral activity. These viral, host genetic signatures and lifestyle interactions may represent a reservoir of biomarkers for early detection, prevention of cancer and rationale-based therapy.