IFNG +874A/T Polymorphism Among Asymptomatic HTLV-1-Infected Individuals Is Potentially Related to a Worse Prognosis.

HTLV-1 infections are persistent and frequently latent; however, productive infections trigger different types of immunological responses that utilize cytokines to control infection. The present study investigated the role of IFNG +874A/T polymorphisms among 153 HTLV-1-infected individuals (33 clinically diagnosed with TSP/HAM, 22 with rheumatologic manifestations, 2 with dermatitis, 1 with uveitis, and 95 asymptomatic patients) and 300 healthy control individuals. Genotyping and proviral HTLV-1 load assessment were performed using real-time PCR assays, and the plasma levels of IFN-γ were measured using an enzyme immunoassay (ELISA). Genotype frequencies were not significantly different, but the presence of the T allele was higher (p < 0.0142) among the asymptomatic patients. Plasma levels of IFN-γ were significantly higher (p < 0.0137) among those with the TT genotype. Their proviral load was also higher, although this elevation did not reach statistical significance. There was no difference in the IFN-γ plasma levels among the symptomatic patients, even when ranked according to disease severity (TSP/HAM or rheumatologic manifestations). However, the difference among asymptomatic patients with the T allele was significantly higher (p < 0.0016) and similar to the plasma levels observed among symptomatic individuals. These results suggest that the IFNG +874A/T polymorphism may modulate the plasma levels of IFN-γ during HTLV-1 infection. Asymptomatic carriers of the polymorphic genotypes appear to develop an inflammatory response in a shorter timeframe, triggering progression to HTLV-1-related symptoms and disorders. These results further suggest that HTLV-1-infected asymptomatic individuals expressing the IFNG +874A/T polymorphism should be monitored more closely in order to readily detect the increase in clinical symptoms, as these patients are potentially at risk of a poor prognosis and should therefore start available treatment procedures earlier.

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Is Not Associated with SNP rs12979860 of the IL-28B Gene.

The present study investigated the association between the rs12979860 polymorphism in the IL-28B gene and HTLV-1 infection as well as the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-infected patients (26 HAM/TSP symptomatic and 53 asymptomatic) and 300 seronegative healthy controls were investigated. Plasma levels of the cytokines TNF-α, TNF-ß, IL-8, IL-10, IL-6, and IFN-γ from infected patients were measured using an indirect enzyme-linked immunosorbent assay. The HTLV proviral load was measured using a real-time PCR assay, and T-cell subset counts were determined by flow cytometry. Real-time PCR was used to genotype the rs12979860 SNP. The allelic and genotypic distributions displayed no significant differences among the investigated groups. No significant association between the serum cytokine levels and the presence of the rs12979860 SNP in symptomatic and asymptomatic subjects was observed. A positive correlation (p = 0.0015) between TNF-ß and IFN-γ was observed in the asymptomatic group, but a positive correlation was only observed (p = 0.0180) between TNF-α and IL-6 in the HAM/TSP group. The proviral load was significantly higher in HAM/TSP patients than in asymptomatic subjects. The present results do not support a previous report indicating an association between the SNP rs12979860 and HAM/TSP outcome.

No evidence of association between MBL2A/O polymorphisms and Mycobacterium tuberculosis infection in populations from the Brazilian Amazon region.

The present study investigated the prevalence of the polymorphisms in the exon 1 of the MBL2 gene in patients with tuberculosis at a hospital in northern Brazil, which is a regional reference for the treatment of the disease. The study group was composed of 167 patients with tuberculosis, 34 of which had the extra-pulmonary form of the disease, while the other 133 had the pulmonary type. The control group consists of 159 healthy individuals. Samples of DNA extracted from leucocytes were submitted to Polymerase Chain Reaction for the amplification of a 120-bp segment of exon 1 of the MBL2 gene. The distribution of allele and genotype frequencies varied little among the different groups, and it was not possible to establish any clear association between the variants of the MBL2 gene and the susceptibility to or clinical profile of tuberculosis infections in the population analyzed.

Human JCV infections as a bio-anthropological marker of the formation of Brazilian Amazonian populations.

JC polyomavirus (JCV) is a member of the Polyomaviridae family. It presents a tropism to kidney cells, and the infection occurs in a variety of human population groups of different ethnic background. The present study investigated the prevalence of JCV infection among human populations from the Brazilian Amazon region, and describes the molecular and phylogenetic features of the virus. Urine samples from two urban groups of Belém (healthy subjects), one Brazilian Afro-descendant "quilombo" from the Rio Trombetas region, and native Indians from the Wai-Wai, Urubu-Kaapor, Tembé, Assurini, Arara do Laranjal, Aukre, Parakanã, Surui and Munduruku villages were investigated for the presence of the virus by amplifying VP1 (230 bp) and IG (610 bp) regions using a polymerase chain reaction. Nucleotide sequences (440 nucleotides, nt) from 48 samples were submitted to phylogenetic analysis. The results confirmed the occurrence of types A (subtype EU), B (subtypes Af-2, African and MY, Asiatic) and C (subtype Af-1) among healthy subjects; type B, subtypes Af-2 and MY, among the Afro-Brazilians; and type B, subtype MY, within the Surui Indians. An unexpected result was the detection of another polyomavirus, the BKV, among Afro-descendants. The present study shows, for the first time, the occurrence of JC and BK polyomaviruses infecting humans from the Brazilian Amazon region. The results show a large genetic variability of strains circulating in the region, infecting a large group of individuals. The presence of European, Asiatic and African subtypes associated to the ethnic origin of the population samples investigated herein, highlights the idea that JCV is a fairly good marker for studying the early migration of human populations, reflecting their early and late history. Furthermore, the identification of the specific mutations associated to the virus subtypes, suggests that these mutations have occurred after the entrance of the virus in the Amazon region of Brazil.

IFNG +874T/A polymorphism and cytokine plasma levels are associated with susceptibility to Mycobacterium tuberculosis infection and clinical manifestation of tuberculosis.

Regarding the importance of interferon-gamma (IFN-gamma) in protective immunity against Mycobacterium tuberculosis and the functional role of IFNG +874T/A single nucleotide polymorphism (SNP) in the IFN-gamma production, the present study investigated the relationship of this genetic polymorphism with susceptibility to tuberculosis (TB). A total of 129 patients with pulmonary tuberculosis (PTB), 33 with extrapulmonary tuberculosis (EPTB), and 156 control subjects were studied. Blood samples were drawn and plasma was used to measure IFN-gamma serum concentration by enzyme-linked immunoassay. DNA samples were extracted from leukocytes and used to investigate +874T/A polymorphism in IFNG gene using allele-specific oligonucleotide-polymerase chain reaction. An association between the presence of the allele +874A and the genotype +874AA with the active tuberculosis was found (p < 0.0001, 95% confidence interval = 1.64-3.22), at the same time that allele + 874T and genotype +874T/T were more frequent in the control group. The average plasma concentration of IFN-gamma among patients with tuberculosis was significantly lower than in the control group, and were lower in the EPTB group than in the group with PTB, suggesting a relationship of low plasma levels of this cytokine with active tuberculosis and the progression to more serious forms of the disease. Furthermore, we observed the association of the +874T/T and +874A/A genotypes with high and low IFN-gamma plasma concentrations, respectively, both in TB patients and in the control groups. Thus our findings suggest an association of the IFNG +874T/A polymorphism with susceptibility to M. tuberculosis infection in the studied population.

Molecular epidemiology of HIV type 1 in northern Brazil: identification of subtypes C and D and the introduction of CRF02_AG in the Amazon region of Brazil.

The molecular epidemiology of HIV-1 strains circulating in Belem-PA and Macapa-AP, in the Northern region of Brazil, is described using sequences of the C2V3 segment of the env and the pro gene of HIV-1 from patients of the Reference Unit for Special Infectious and Parasitary Diseases (URE-DIPE) in Belem-PA and the Central Laboratory (LACEN) in Macapa-AP. Subtype B was the most frequently found in relation to pro (88.3%) in Belem and in Macapa (97.1%) and env (88.3% in Belem and 100% in Macapa). Subtype F was also described in Belem (9.3% pro and 8.3% env) and Macapa (2.8% pro). Subtype D was described for the first time in the Northern region of the country as well as the recent entry of CRF02_AG. Furthermore, several possible recombinant forms among the various subtypes were found in both cities. The results support the hypothesis that HIV-1 infection is associated with the epidemic of the virus in the Southeast region of the country and that the city of Belem is the most important route for HIV-1 entry in the Northern region of Brazil.

[Molecular characterization of HTLV-1 among patients with tropical spastic paraparesis/HTLV-1 associated myelopathy in Belém, Pará]. / Caracterização molecular do HTLV-1 em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV-1 em Belém, Pará.

The present study evaluated the occurrence of HTLV-1 and its subtypes in blood samples of patients presenting symptoms of tropical spastic paraparesis/HTLV-1 associated myelopathy. The detection of HTLV infection was performed by serological and molecular assays. Five patients were infected by HTLV-1 of the Cosmopolitan subtype, subgroup Transcontinental. The results confirm the occurrence of HTLV-1 infection among patients with clinical diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy in Belém, Pará.

Caracterização molecular do HTLV-1 em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV-1 em Belém, Pará / Molecular characterization of HTLV-1 among patients with tropical spastic paraparesis/HTLV-1 associated myelopathy in Belém, Pará

O presente estudo avaliou a ocorrência da infecção pelo HTLV-1 e seus subtipos em amostras de sangue de pacientes com diagnóstico clínico de paraparesia espástica tropical/mielopatia associada ao Htlv-1. A detecção da infecção pelo HTLV realizou-se através de testes sorológico e molecular. Cinco amostras estavam infectadas pelo HTLV-1 do subtipo Cosmopolita, subgrupo Transcontinental. Os resultados obtidos confirmam a ocorrência de infecção pelo HTLV-1 em pacientes com diagnóstico clínico de paraparesia espástica tropical/mielopatia associada ao Htlv-1em Belém, Pará.

The present study evaluated the occurrence of HTLV-1 and its subtypes in blood samples of patients presenting symptoms of tropical spastic paraparesis/HTLV-1 associated myelopathy. The detection of HTLV infection was performed by serological and molecular assays. Five patients were infected by HTLV-1 of the Cosmopolitan subtype, subgroup Transcontinental. The results confirm the occurrence of HTLV-1 infection among patients with clinical diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy in Belém, Pará.

Serological and molecular typing of HIV type 1 infection in the Tiriyo tribe, a native Indian community of the Amazon region of Brazil.

The seroprevalence and the occurrence of an HIV-1 subtype was assessed in blood samples of the Tiriyo tribe. Antibody was found in 0.6% and the molecular analysis of the pro region detected the emergence of a subtype B for the first time in a native Indian tribe of the Amazon region of Brazil.

Serological and molecular evidence of HTLV-I infection among Japanese immigrants living in the Amazon region of Brazil.

Human T-lymphotropic virus type I (HTLV-I) infection was investigated in 168 Japanese immigrants (64 males and 104 females) living in the Tome-Acu county located in the State of Para, Brazil. The serological screening was performed using an enzyme-linked immunosorbent assay, and showed the presence of anti-HTLV in four women whose ages ranged from 50 to 88. Confirmation of infection and discrimination HTLV typing was performed using a nested PCR on the extracted DNA targeting the pX region. In three of the samples, infection was confirmed to be HTLV-I. Sequencing HTLV-I 5'LTR and the RFLP pattern using DraI and SacI endonucleases indicated that the virus is a member of the Cosmopolitan group. These three women originated from the Kyushu region, though two of the corresponding HTLV-I strains were phylogenetically related to the Japanese subgroup and the third to the Transcontinental subgroup, which probably reflects the geographical origin of the infected individuals. The Japanese community residing in the northern Brazil apparently have not contributed to increase the prevalence of HTLV-I in the country.

Molecular epidemiology of human T-lymphotropic virus type II infection in Amerindian and urban populations of the Amazon region of Brazil.

Molecular characterization of human T-cell lymphotropic virus II (HTLV-II) isolates in North America and Europe has shown the existence of two principal subtypes of the virus, HTLV-IIa and HTLV-IIb. Subsequent studies on HTLV-II isolates from Brazil have suggested the existence of a unique variant phylogenetically related to HTLV-IIa but phenotypically similar to HTLV-IIb with respect to the transactivatory protein, Tax. This variant has been designated HTLV-IIc. To better clarify the variability and distribution of HTLV-II in Brazil, the viruses present in two population groups from the Amazon region were tested for the presence of HTLV-II using serological and molecular assays. The groups consisted of blood donors from three Amerindian communities and of HIV-1/HTLV-II coinfected patients residing in Belém, an urban area. Nucleotide sequences and phylogenetic analysis confirmed the presence of HTLV-IIc subtype among Amerindian populations and, for the first time, the presence of the same virus among urban groups in Belém. The isolated occurrence of the HTLV-IIc subtype among Amerindian populations in the Amazon region could be attributed to (1) the different migratory pathways and founder effect, or (2) the local origin of a proto-HTLV-II carried by Amerindian ancestors who migrated to the Amazon circa 11,000 to 13,000 years ago. These results suggest that not only is HTLV-IIc unique to this region, but that its presence in urban areas of Brazil has resulted from admixture processes during the colonization of the country.