Sexual transmission of human T-cell lymphotropic virus type 1

Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in many parts of the world and is primarily transmitted through sexual intercourse or from mother to child. Sexual transmission occurs more efficiently from men to women than women to men and might be enhanced by sexually transmitted diseases that cause ulcers and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2), and chancroid. Other sexually transmitted diseases might result in the recruitment of inflammatory cells and could increase the risk of HTLV-1 acquisition and transmission. Additionally, factors that are associated with higher transmission risks include the presence of antibodies against the viral oncoprotein Tax (anti-Tax), a higher proviral load in peripheral blood lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fluid has been reported to increase HTLV replication and transmission, whereas male circumcision and neutralizing antibodies might have a protective effect. Recently, free virions were discovered in plasma, which reveals a possible new mode of HTLV replication. It is unclear how this discovery might affect the routes of HTLV transmission, particularly sexual transmission, because HTLV transmission rates are significantly higher from men to women than women to men.FINANCIAL SUPPORT Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Fundação Faculdade de Medicina (FFM)

Human T-Lymphotropic viruses evolution possibly explained by primate deltaretrovirus geographical segregation

The primate T cell lymphotropic virus group comprises pathogenic and apathogenic agents found in human and simian hosts. Up to date, three types of the simian T cell lymphotropic virus/STLV and four types of the human T cell lymphotropic virus/HTLV have been isolated and characterized from non human primates and from human hosts respectively. We have not found evidences of STLV-1 infection among new world monkeys and besides findings of HTLV-1 and HTLV-2 infection among brazilian mixed ethnic populations and Amerindians respectively, some unresolved HTLV indeterminate-Western blot results prevailed among human groups of different ethnic background. Based on recent serologic detection, isolation and characterization of HTLV-3 and HTLV-4 among African populations in central Africa and additional unrefutable evidences of early human migration from Africa and Australia to the American continent previously of Asiatic population migration lead us to hypothesize that human descendents of mixed Amerinds and Africans or remaining Africans explain the very frequent presence of Western blot-indeterminate results for HTLV-1/2 that we and other groups have been detecting and also the unusual absence of HTLV-2 infection among some relatively homogeneous ethnic native human populations in the American continent

Prevalence of anxiety, depression and quality of life in HTLV-1 infected patients

The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and\ud sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting\ud on quality of life. Objective: The purpose of this study was to evaluate the frequency of\ud depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients.\ud Material and Methods: This was a cross-sectional study including 67 asymptomatic (control group)\ud and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales\ud for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality\ud of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the\ud disability level (Osame’s Disability Status Scale). All patients had HTLV-I diagnosis by serological\ud and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to\ud July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman\ud correlation test. Data among groups were analyzed and correlated with functional and severity aspects.\ud Results: The results showed that patients with HAM/TSP compared to asymptomatic carriers\ud had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of\ud life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment\ud (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of\ud the WHOQOL-brief were: education, family income and social class. Conclusion: A well conducted\ud evaluation and counseling may help in treatment, for a better quality of life of these patients.Financial Support: FAPESP e Coordenadoria de Controle de Doenças CCD/SES-SP

Molecular characterization of human T-cell lymphotropic virus type 1 full and partial genomes by Illumina massively parallel sequencing technology.

Background\ud \ud Here, we report on the partial and full-length genomic (FLG) variability of HTLV-1 sequences from 90 well-characterized subjects, including 48 HTLV-1 asymptomatic carriers (ACs), 35 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 7 adult T-cell leukemia/lymphoma (ATLL) patients, using an Illumina paired-end protocol.\ud Methods\ud \ud Blood samples were collected from 90 individuals, and DNA was extracted from the PBMCs to measure the proviral load and to amplify the HTLV-1 FLG from two overlapping fragments. The amplified PCR products were subjected to deep sequencing. The sequencing data were assembled, aligned, and mapped against the HTLV-1 genome with sufficient genetic resemblance and utilized for further phylogenetic analysis.\ud Results\ud \ud A high-throughput sequencing-by-synthesis instrument was used to obtain an average of 3210- and 5200-fold coverage of the partial (n = 14) and FLG (n = 76) data from the HTLV-1 strains, respectively. The results based on the phylogenetic trees of consensus sequences from partial and FLGs revealed that 86 (95.5%) individuals were infected with the transcontinental sub-subtypes of the cosmopolitan subtype (aA) and that 4 individuals (4.5%) were infected with the Japanese sub-subtypes (aB). A comparison of the nucleotide and amino acids of the FLG between the three clinical settings yielded no correlation between the sequenced genotype and clinical outcomes. The evolutionary relationships among the HTLV sequences were inferred from nucleotide sequence, and the results are consistent with the hypothesis that there were multiple introductions of the transcontinental subtype in Brazil.\ud Conclusions\ud \ud This study has increased the number of subtype aA full-length genomes from 8 to 81 and HTLV-1 aB from 2 to 5 sequences. The overall data confirmed that the cosmopolitan transcontinental sub-subtypes were the most prevalent in the Brazilian population. It is hoped that this valuable genomic data will add to our current understanding of the evolutionary history of this medically important virus.This study was supported with funding from the Fundação de Amparo a Pesquisa do Estado de São Paulo (2011/12297-2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

HERV-W/MRSV envelope transcripts detection\ud in blood of multiple sclerosis patients after\ud Natalizumab treatment

FAPESP 2010/10619-

Aquaporin-4 Antibodies Are Not Related to HTLV-1\ud Associated Myelopathy

Introduction: The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high among Brazilians (,1:200).\ud HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the most common neurological complication of\ud HTLV-1 infection. HAM/TSP can present with an acute/subacute form of longitudinally extensive myelitis, which can be\ud confused with lesions seen in aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorders (NMOSD)\ud on MRI. Moreover, clinical attacks in patients with NMOSD have been shown to be preceded by viral infections in around\ud 30% of cases.\ud Objective: To evaluate the frequency of AQP4-Ab in patients with HAM/TSP. To evaluate the frequency of HTLV-1 infection\ud in patients with NMOSD.\ud Patients and Methods: 23 Brazilian patients with HAM/TSP, 20 asymptomatic HTLV-1+ serostatus patients, and 34 with\ud NMOSD were tested for AQP4-Ab using a standardized recombinant cell based assay. In addition, all patients were tested for\ud HTLV-1 by ELISA and Western blotting.\ud Results: 20/34 NMOSD patients were positive for AQP4-Ab but none of the HAM/TSP patients and none of the\ud asymptomatic HTLV-1 infected individuals. Conversely, all AQP4-Ab-positive NMOSD patients were negative for HTLV-1\ud antibodies. One patient with HAM/TSP developed optic neuritis in addition to subacute LETM; this patient was AQP4-Ab\ud negative as well. Patients were found to be predominantly female and of African descent both in the NMOSD and in the\ud HAM/TSP group; Osame scale and expanded disability status scale scores did not differ significantly between the two\ud groups.\ud Conclusions: Our results argue both against a role of antibodies to AQP4 in the pathogenesis of HAM/TSP and against an\ud association between HTLV-1 infection and the development of AQP4-Ab. Moreover, the absence of HTLV-1 in all patients\ud with NMOSD suggests that HTLV-1 is not a common trigger of acute attacks in patients with AQP4-Ab positive NMOSD in\ud populations with high HTLV-1 seroprevalence.This study received financial support from the Brazilian government agencies FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo - www. fapesp.br/en) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - www.capes.gov.br). The work of S.J. and B.W. was supported by research grants from Bayer Schering Healthcare and from Merck Serono. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Difficulties in diagnosing atypical primary HIV-1 infection

Muitos casos de infecção primária pelo HIV não são identificados devido a dificuldades em seu diagnóstico clínico e laboratorial. Este trabalho relata um caso atípico de infecção primária pelo HIV em um usuário de drogas intravenosas que apresentou como primeira manifestação clínica, quadro agudo de hepatite. A pesquisa de anticorpos dirigidos contra vários vírus inclusive o HIV, resultou negativa, na primeira análise do soro do paciente. No entanto, o diagnóstico de infecção primária pelo HIV foi sugerido inicialmente utilizando um novo método laboratorial alternativo para a pesquisa destes anticorpos, denominado IVIAP (in vitro induced antibody production). A infecção HIV foi confirmada pela antigenemia p24 na mesma amostra de sangue e aparecimento de anticorpos específicos em amostras sequenciais de soro do paciente. Os autores deste trabalho sugerem a potencial utilização da IVIAP e de outros exames laboratoriais complementares para o diagnóstico de infecção primária aguda pelo HIV, em populações expostas a situação de risco para adquirir a infecção.Several cases of primary HIV-1 infection are not identified, either because the diagnosis is not suspected or because they test negative for HIV-1 antibody. This work presents an uncommon case of primary HIV-1 infection in an young parenteral drug abuser man, who presented symptoms of acute hepatitis. During the initial acute phase the serum sample of the patient tested negative for the presence of antibodies against several viruses, including HIV-1. Nevertheless, the diagnosis of primary HIV-1 infection was suspected by using an alternative method for"in vitro" induced antibody production (IVIAP), and confirmed by p24 antigen serum positivity and seroconversion in serial plasma samples of the patient. The authors suggest the use of the IVIAP and others complementary assays to help the diagnosis of acute HIV-1 infection in persons at high risk conditions

Difficulties in diagnosing atypical primary HIV-1 infection

Several cases of primary HIV-1 infection are not identified, either because the diagnosis is not suspected or because they test negative for HIV-1 antibody. This work presents an uncommon case of primary HIV-1 infection in an young parenteral drug abuser man, who presented symptoms of acute hepatitis. During the initial acute phase the serum sample of the patient tested negative for the presence of antibodies against several viruses, including HIV-1. Nevertheless, the diagnosis of primary HIV-1 infection was suspected by using an alternative method for"in vitro" induced antibody production (IVIAP), and confirmed by p24 antigen serum positivity and seroconversion in serial plasma samples of the patient. The authors suggest the use of the IVIAP and others complementary assays to help the diagnosis of acute HIV-1 infection in persons at high risk conditions