Diagnóstico molecular de vírus T-linfotrópico humano (HTLV): histórico e estado da arte
pdf

Palavras-chave

vírus T-linfotrópico humano (HTLV); vírus T-linfotrópico humano 1 (HTLV-1); vírus T-linfotrópico 2 (HTLV-2); Diagnóstico; Técnicas de amplificação de ácidos nucleicos (NAAT); Reação em cadeia da polimerase (PCR).

Como Citar

1.
Caterino-de-Araujo A, Gonçalves MG. Diagnóstico molecular de vírus T-linfotrópico humano (HTLV): histórico e estado da arte. Bepa [Internet]. 14º de julho de 2022 [citado 26º de dezembro de 2024];18(212). Disponível em: https://periodicos.saude.sp.gov.br/BEPA182/article/view/36571

Resumo

Técnicas de amplificação de ácidos nucleicos (nucleic acid amplification techniques, NAATs) que pesquisam partes do genoma proviral de vírus T-linfotrópicos humanos (human T-lymphotropic virus, HTLVs) são importantes ferramentas para a caracterização molecular, diagnóstico e quantificação de carga proviral. No Brasil, os HTLV-1 e HTLV-2 são endêmicos, e o diagnóstico diferencial entre eles é de suma importância, uma vez que o HTLV-1 está relacionado a doenças graves como a mielopatia associada ao HTLV-1 e a leucemia/linfoma de células T adultas, enquanto o HTLV-2 parece não ser patogênico. Este trabalho faz uma revisão narrativa das NAATs utilizadas ao longo dos anos na pesquisa de HTLVs; apresenta um quadro com dados de autor/ano de publicação, local de realização do trabalho, técnica empregada, genes alvo e objetivo do estudo. Outrossim, relata causas de possíveis falhas no diagnóstico molecular; apresenta novas metodologias e pesquisas sobre técnicas que mais se adequam à realidade brasileira; esclarece sobre a necessidade de se implantar o diagnóstico molecular na rede pública de saúde, tomando como base seu melhor custo-benefício para laboratórios que dispõem de infraestrutura e pessoal capacitado. Concluindo, fornece informações úteis para a implementação de políticas públicas de saúde dentro do âmbito do SUS, uma vez que a infecção por HTLV-1 vem ganhando notoriedade junto ao Ministério da Saúde do Brasil e a Organização Mundial da Saúde, por ser de alta prevalência, estar associada a doenças de alta morbidade e letalidade, carecer de cura, e só ser controlada com medidas de prevenção da infecção que dependem do diagnóstico.

https://doi.org/10.57148/bepa.2021.v.18.36571
pdf

Referências

Caterino-de-Araujo A, Barbosa-Stancioli EF, Alonso Neto JB,

Aragón MG, Galvão-Castro B, Ishak R, et al. Laboratory

diagnosis of HTLV in Brazil: assays, flowcharts, challenges

and perspectives. Rev Soc Bras Med Trop. 2021; 54:

e0175-2021. https://doi.org/10.1590/0037-8682-0175-2021

Jacob F, Santos-Fortuna E, Azevedo RS, Caterino-de-Araujo A.

Serological patterns for HTLV-I/II and its temporal trend

in high-risk populations attended at Public Health Units

of São Paulo, Brazil. J Clin Virol. 2008:42(2):

-55, 2008. https://doi.org/10.1016/j.jcv.2008.01.017

Caterino-de-Araujo A, Campos KR, Petrucci TVB, da Silva RX,

Lemos MF, Moreira RC. Surveillance of human retroviruses

in blood samples from patients with hepatitis B and C in São

Paulo, Brazil. Rev Soc Bras Med Trop. 2020; 53:e20190378.

https://doi.org/10.1590/0037-8682-0378-2019

Campos KR, Gonçalves MG, Costa NA, Caterino-de-Araujo A.

Comparative performances of serologic and molecular

assays for detecting HTLV-1 and HTLV-2 in patients

infected with HIV-1. Brazilian J Infect Dis. 2017;21(3):

-305. https://doi.org/10.1016/j.bjid.2017.02.005

Campos KR, Santos FLN, Brito VS, Gonçalves NLS, Araujo THA,

Galvão-Castro B, et al. Line immunoassay for confirmation and

discrimination of human T-cell lymphotropic virus infections in

inconclusive Western blot serum samples from Brazil. J Clin Microbiol.

;58(1):e01384-19. https://doi.org/10.1128/JCM.01384-19

Okuma K, Kuramitsu M, Niwa T, Taniguchi T, Masaki Y, Ueda G,

et al. Establishment of a novel diagnostic test algorithm for human

T-cell leukemia virus type 1 infection with line immunoassay

replacement of western blotting: a collaborative study for

performance evaluation of diagnostic assays in Japan. Retrovirology.

;17(1):26. https://doi.org/10.1186/s12977-020-00534-0

ICTV, Comitê Internacional de Taxonomia Viral (CITV)

Taxonomy - International Committee on Taxonomy of

Viruses (ICTV). Acessado em 30 de maio de 2020.

Disponível em: https://talk.ictvonline.org/taxonomy.

Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD,

Gallo RC. Detection and isolation of type C retrovirus

particles from fresh and cultured lymphocytes of a patient

with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA.

;77(12):7415-9. https://doi.org/10.1073/pnas.77.12.7415

Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I,

Golde D, Gallo RC. A new subtype of human T-cell leukemia virus

(HTLV-II) associated with a T-cell variant of hairy cell leukemia.

Science. 1982;218:571-3. doi: 10.1126/science.6981847.

Bangham CR, Cook LB, Melamed A. HTLV-1 clonality in adult T-cell

leukaemia and non-malignant HTLV-1 infection. Semin Cancer Biol.

;26:89-98. https://doi.org/10.1016/j.semcancer.2013.11.003

Melamed A, Witkover AD, Laydon DJ, Brown R, Ladell K, Miners

K, et al. Clonality of HTLV-2 in natural infection. PLoS Pathog.

;10(3):e1004006. https://doi.org/10.1371/journal.ppat.1004006

Gessain A, Cassar O. Epidemiological aspects and

world distribution of HTLV-1 infection. Front Microbiol.

;3:388. doi:10.3389/fmicb.2012.00388.

Paiva A, Casseb J. Sexual transmission of human T-cell

Lymphotropic virus type 1. Rev Soc Bras Med Trop. 2014;47(3):

-74. http://dx.doi.org/10.1590/0037-8682-0232-2013

Calattini S, Chevalier SA, Duprez R, Bassot S, Froment

A, Mahieux R, et al. Discovery of a new human T-cell

lymphotropic virus (HTLV-3) in Central Africa. Retrovirology

;2:30. https://doi.org/10.1186/1742-4690-2-30

Wolfe ND, Heneine W, Carr JK, Garcia AD, Shanmugam V, Tamoufe

U, et al. Emergence of unique primate T-lymphotropic viruses

among central African bushmeat hunters. Proc Natl Acad Sci USA.

, 102(22):7994-9. https://doi.org/10.1073/pnas.0501734102

Ministério da Saúde (MS). Secretaria de Vigilância

em Saúde. Prevalência da infecção por HTLV-1/2

no Brasil. Boletim Epidemiológico. Volume 51 | Nº

| Nov. 2020. p.25-33. ISSN: 2358-9450

Ministério da Saúde (MS). Portaria 1.376, de novembro de 1993.

Diário Oficial da União, Brasília, 2 de dezembro de 1993. [Aprov a

alterações na Portaria n. 721/GM, de 9 de ago. 1989, que aprova

normas técnicas para coleta, processamento e transfusão de

sangue, componentes e derivados, e dá outras providências].

Ministério da Saúde (MS). Portaria 2.600, de 21 de outubro de

Diário Oficial da União, Brasília. [Aprova o Regulamento

Técnico do Sistema Nacional de Transplantes].

Proietti AB de FC. HTLV Cadernos Hemominas, Vol. 16. Minas

Gerais: Belo Horizonte: Fundação Centro de Hematologia

e Hemoterapia de Minas Gerais; 2015. Disponível em:

http://www.hemominas.mg.gov.br/publicacoes

Futsch N, Mahieux R, Dutartre H. HTLV-1, the other pathogenic

yet neglected human retrovirus: from transmission to therapeutic

treatment. Viruses 2018;10(1):1. doi:10.3390/v10010001.

Mesnard J-M, Barbeau B, Césaire R, Péloponèse J-M. Roles of

HTLV-1 basic zip factor (HBZ) in viral chronicity and

leukemic transformation. Potential new therapeutic

approaches to prevent and treat HTLV-1-related diseases.

Viruses 2015;7:6490–505. doi:10.3390/v7122952

Seiki M, hattori S, Hirayama Y, Yoshida M. Human adult T-cell

leukemia virus: complete nucleotide sequence of the provirus

genome integrated in leukemia cell DNA. Proc Natl Acad Sci

USA. 1983:80:3618-22. doi: 10.1073/pnas.80.12.3618

Shimotohno K, Wachsman W, Takahashi Y, Golde DW,

Miwa M, Sugimura T, et al. Nucleotide sequence of the 3’

region of an infectious human T-cell leukemia virus type II

genome. Proc Natl Acad Sc. USA. 1984;81:6657-61, 1984.

https://www.pnas.org/content/pnas/81/21/6657.full.pdf

Haseltine WA, Sodroski J, Patarca R, Briggs D, Perkins D,

Wong-Staal F. Structure of 3’ terminal region of type II human

T lymphotropic virus: evidence for new coding region. Science

;225:419-21, 1984. doi: 10.1126/science.6330894

Shimotohno K, Takahashi Y, Shimizu N, Gojobori T, Golde DW,

Chen ISY, et al. Complete nucleotide sequence of an infectious

clone of human T-cell leukemia virus type II: an open reading

frame for the protease gene. Proc Natl Acad Sci USA. 1985;82:

-5. https://www.pnas.org/content/pnas/82/10/3101.full.pdf

Malik KT, Even J, Karpas A. Molecular cloning and complete

nucleotide sequence of an adult T-cell leukemia virus/human T-cell

leukemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin:

relationship to other members of the ATLV/HTLV-I subgroup. J Gen

Virol. 1988;69:1695-710. https://doi.org/10.1099/0022-1317-69-7-1695

Erlich HA. Polymerase chain reaction. J Clin Immunol. 1989;9:

-47. https://link.springer.com/article/10.1007/BF00918012

Komurian-Pradel F, Pelloquin F, Sonoda S, Osame M, de Thé

G. Geographical subtypes demonstred by RFLP following

PCR in the LTR region of HTLV-I. AIDS Res Hum Retroviruses

;8(4):429-34. https://doi.org/10.1089/aid.1992.8.429

Vidal AU, Gessain A, Yoshida M, Mahieux R, Nishioka K,

Tekaia F, et al. Molecular epidemiology of HTLV type I in Japan:

evidence for two distinct ancestral lineages with a particular

geographical distribuition. AIDS Res Hum Retroviruses

;10(11):1557-66. https://doi.org/10.1089/aid.1994.10.1557

Vidal AU, Gessain A, Yoshida M, Tekaia F, Garin B, Guillemain B, et al.

Phylogenetic classification of human T cell leukaemia/lymphoma vírustype I genotypes in five major molecular and geographicalsubtypes. J Gen Virol. 1994;75(12): 3655-66.https://doi.org/10.1099/0022-1317-75-12-3655

Heneine W, Khabbaz RF, Lal RB, Kaplan JE. Sensitive and

specific polymerase chain reaction assays for diagnosis of

human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II

infections in HTLV-I/II seropositive individuals. J Clin Microbiol.

;30:1605-7. doi: 10.1128/jcm.30.6.1605-1607.1992

De-Araujo AC, Casseb JSR, Neitzert E, Xavier de Souza ML,

Mammano F, Del Mistro A, et al. HTLV-1 and HTLV-2 infections among

HIV-1 seropositive patients in São Paulo, Brazil. Eur J Epidemiol.

;10:165-71. https://link.springer.com/article/10.1007/BF01730366

Garin B, Gosselin S, de The G, Gessain A. HTLV-I/II infection

in a high viral endemic area of Zaire, Central Africa:

comparative evaluation of serology, PCR, and significance

of indeterminate Western Blot pattern. J Med Virol.

;44:104-9. https://doi.org/10.1002/jmv.1890440119

Vallejo A, Garcia-Saiz A. Typing human T-cell lymphotropic virus

(HTLV-I and HTLV-II) by nested polymerase chain reaction:

application to clinical specimens. J Virol Methods 1995;51:

-18. https://doi.org/10.1016/0166-0934(94)00093-V

Soldan SS, Graf MD, Waziri A, Flerlage AN, Robinson SM,

Kawanishi T, et al. HTLV-I/II seroindeterminate Western blot

reactivity in a cohort of patients with neurological disease.

J Infect Dis. 1999; 180:685-694. doi: 10.1086/314923

Poiesz BJ, Dube S, Choi D, Esteban E, Ferrer J, Leon-Ponte

M, et al. Comparative performances of an HTLV-I/II EIA and

other serologic and PCR assays on samples from persons

at risk for HTLV-II infection. Transfusion 2000;40:924-30.

https://doi.org/10.1046/j.1537-2995.2000.40080924.x

Costa JMP, Sumita LM, Segurado AC. Non-radioisotope detection

of pol sequences of HTLV-1 proviral DNA: Standardization

and sensitivity analysis. J Virol Methods 2006;137: 29-33.

https://doi.org/10.1016/j.jviromet.2006.05.026

Costa JMP, Segurado AC. Molecular evidence of human T-cell

lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) infections

in HTLV seroindeterminate individuals from São Paulo, Brazil.

J Clin Virol. 2009;44:185-9. doi: 10.1016/j.jcv.2008.12.015

Matsumoto C, Mitsunaga S, Oguchi T, Motomi Y, Shimada T,

Ichigawa A, et al. Detection of human T-cell leukemia virus

type I (HTLV-I) provirus in an infected cell line and in peripheral

mononuclear cells of blood donors by the nested double

polymerase chain reaction method: comparison with HTLV-I

antibody tests. J Virol. 1990;64(11):5290-4. https://www.ncbi.nlm.

nih.gov/pmc/articles/PMC248573/pdf/jvirol00066-0068.pdf

Caterino-de-Araujo A, Santos-Fortuna E, Zandoná-Meleiro

MC, Suleiman J, Calabrò ML, Favero A, et al. Sensitivity of

two ELISA tests in relation to western blot in detecting HTLV-1

and HTLV-2 infections among HIV-1-infected patients from São

Paulo, Brazil. Diagn Microbiol Infect Dis. 1998;30(3):173‑82.

https://doi.org/10.1016/S0732-8893(97)00236-8

Mangano AM, Remesar M, del Pozo A, Sen L. Human T

lymphotropic virus types I and II proviral sequences in Argentinian

blood donors with indeterminate Western blot patterns. J Med

Virol. 2004;74:323-7. https://doi.org/10.1002/jmv.20172

Morimoto HK, Morimoto AA, Reiche EMV, Ueda LT, Matsuo

T, Reiche FV, et al. Difficulties in the diagnosis of HTLV‑2

infection in HIV/AIDS patients from Brazil. Comparative

performances of serologic and molecular assays, and

detection of HTLV-2b subtype. Rev Inst Med Trop S. Paulo.

;49(4):225-30. doi: 10.1590/s0036-46652007000400006

Zanjani DS, Shahabi M, Talaei N, Afzalaghaee M, Tehranian F,

Bazargani R. Molecular analysis of human T cell lymphotropic

virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from

Northeast Iran: Evidence of proviral tax, env, and gag sequences. AIDS

Res Hum Retroviruses 2011;27:131-5. doi: 10.1089/aid.2010.0017

Tuke PW, Luton P, Garson JA. Differential diagnosis of

HTLV-I and HTLV-II infections by restriction enzyme analysis

of “nested” PCR products. J Virol Methods 1992;40:163‑73.

https://doi.org/10.1016/0166-0934(92)90065-L

Gallego S, Mangano A, Gastaldello R, Sem L, Medeot S.

Usefulness of a nested-polymerase chain reaction for

molecular diagnosis of human T-cell lymphotropic virus

type I/II. Mem Inst Oswaldo Cruz, R Janeiro. 2004;99(4):377‑80.

https://doi.org/10.1590/S0074-02762004000400006

Vallinoto ACR, Muto NA, Pontes GS, Machado LFA, Azevedo VN,

Santos SEB, et al. Serological and molecular evidence

of HTLV-1 infection among Japanese immigrants living in

the Amazon region of Brazil. Jpn J Infect Dis. 2004;57:

-9. https://www.niid.go.jp/niid/images/JJID/57/156.pdf

Laurentino RV, Lopes IGL, Azevedo VN, Machado LF,

Moreira MR, Lobato L, et al. Molecular characterization

of human T-cell lymphotropic virus coinfecting human

immunodeficiency virus 1 infected patients in the Amazon

region of Brazil. Mem Inst Oswaldo Cruz. 2005;100:

-6. doi: 10.1590/s0074-02762005000400006

Vallinoto ACR, Pontes GS, Muto NA, Lopes IG, Machado LF,

Azevedo VN, et al. Identification of human T-cell lymphotropic

virus infection in a semi-isolated afro-brazilian quilombo

located in the Marajó island (Pará, Brazil). Mem Inst Oswaldo Cruz,

R Janeiro. 2006;101:103-5. doi: 10.1590/s0074-02762006000100020

Souza LA, Lopes IGL, Maia EL, Azevedo VN, Machado LFA, Ishak

MOG, et al. Caracterização molecular do HTLV-1 em pacientes

com paraparesia espástica tropical/mielopatia associada ao HTLV-1

em Belém, Pará. Rev Soc Bras Med Trop. 2006;39(5):

-6. https://www.scielo.br/pdf/rsbmt/v39n5/a17v39n5.pdf

Berini CA, Eirin ME, Pando MA, Biglione MM. Human T-cell

lymphotropic virus types I and II (HTLV-I and -II) infection among

seroindeterminate cases in Argentina. J Med Virol. 2007;79:

-73. https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.20731

Casseb J, Posada-Vergara MP, Montanheiro P, Fukumori LMI,

Olah I, Smid J, et al. T CD4+ cells count among patients co-infected

with human Immunodeficiency virus type 1 (HIV-1) and human

T-cell leukemia virus type 1 (HTLV-1): high prevalence of tropical

spastic paraparesis / HTLV-1-associated myelopathy (TSP/HAM).

Rev Inst Med trop S. Paulo. 2007; 49(4):

-3. https://doi.org/10.1590/S0036-46652007000400007

Ishak R, Vallinoto ACR, Azevedo VN, Vicente ACP, Hall WW,

Ishak MOG. Molecular evidence for infection by HTLV-2

among individuals with negative serological screening

tests for HTLV antibodies. Epidemiol Infect. 2007;135:

-9. https://doi.org/10.1017/S0950268806006984

Zehender G, Ebranati E, Bernini F, De Maddalena C, Giambelli

C, Collins J, et al. Phylogeny of human T cell lymphotropic

virus type 1 in Peru: a high degree of evolutionary relatedness

with South African isolates. AIDS Res Hum Retroviruses

;23(9):1146-9. https://doi.org/10.1089/aid.2007.0039

Montanheiro P, Olah I, Fukumori LMI, Smid J, Oliveira ACP, Kanzaki

LIB, et al. Low DNA HTLV-2 proviral load among women in São Paulo

City. Virus Res. 2008;135:22-5. doi:10.1016/j.virusres.2008.01.015

Olah I, Fukumori LMI, Smid J, Penalva de Oliveira AC, Duarte

AJS, Casseb J. Neither molecular diversity of envelope,

immunosuppression status, nor proviral load causes indeterminate

HTLV Western blot profiles in samples from human T-cell

lymphotropic virus type 2 (HTLV-2)-infected individuals. J Med

Virol. 2010;82:837-42. https://doi.org/10.1002/jmv.21718

Costa EAS, Magri MC, Caterino-de-Araujo A. The best

algorithm to confirm the diagnosis of HTLV-1 and HTLV-2 inat risk individuals from São Paulo, Brazil. J Virol Methods.2011; 173:280-3. doi: 10.1016/j.jviromet.2011.02.018

De Oliveira EH, Oliveira-Filho AB, Souza LA, Silva LV, Ishak

MOG, Ishak R, et al. Human T-cell lymphotropic virus in patients

infected with HIV-1: molecular epidemiology and risk factors

for transmission in Piauí, Northeastern Brazil. Curr HIV Res.

,10(8):700-7. doi: 10.2174/1570162x11209080700.

Berini CA, Eirin ME, Delfino CM, W eissenbacher M, Biglione

MM. Predominance of human lymphotropic T cell virus type 2

subtype b in urban populations of Argentina. AIDS Res Hum

Retrovir. 2012;28(9):1102-9. doi: 10.1089/AID.2011.0311

Costa CA, Furtado KCYO, Ferreira LSCF, Almeida DS,

Linhares AC, Ishak R, et al. Familial transmission of

human T-cell lymphotrophic virus: silent dissemination of

an emerging but neglected infection. PLoS Negl Trop Dis.

;7(6):e2272. doi:10.1371/journal.pntd.0002272

Paiva A, Smid J, Haziot ME, Assone T, Pinheiro S, Fonseca

LAM, et al. High risk of heterosexual transmission of human

T-cell lymphotropic virus type 1 infection in Brazil. J Med

Virol. 2017;89:1287-94. https://doi.org/10.1002/jmv.24745

Vrielink H, Zaaijer HL, Cuypers HTM, van der Poel CL,

Woerdeman M, Lelie PN, et al. Evaluation of a new HTLV-I/

II polymerase chain reaction. Vox Sang. 1997;72:144-7.

https://doi.org/10.1046/j.1423-0410.1997.7230144.x

Liu H, Shah M, Stramer SL, Chen W, Weiblen BJ, Murphy EL.

Sensitivity and specificity of human T-lymphotropic virus (HTLV) types

I and II polymerase chain reaction and several serologic assays in

screening a population with a high prevalence of HTLV-II. Transfusion

;39:1185-93. https://doi.org/10.1046/j.1537-2995.1999.39111185.x

Césaire R, Dehée A, Lézin A, Désiré N, Bourdonné O, Dantin

F, et al. Quantification of HTLV type I and HIV type 1 DNA

load in coinfected patients: HIV type 1 infection does not

alter HTLV type I proviral amount in the peripheral blood

compartment. AIDS Res Hum Retroviruses 2001;17(9):799‑805.

https://doi.org/10.1089/088922201750251990

Estes MC, Sevall JS. Multiplex PCR using real time DNA amplification

for the rapid detection and quantitation of HTLV I or II. Mol Cell

Probes. 2003;17:59-68. doi:10.1016/S0890-8508(03)00002-1

Kamihira S, Dateki N, Sugahara K, Hayashi T, Harasawa

H, Minami S, et al. Significance of HTLV-1 proviral load

quantification by real-time PCR as a surrogate marker for

HTLV-1-infected cell count. Clin Lab Haem. 2003;25:111‑7.

https://doi.org/10.1046/j.1365-2257.2003.00503.x

Lee TH, Chafets DM, Busch MP, Murphy EL. Quantitation of

HTLV-I and II proviral load using real-time quantitative PCR

with SYBR Green chemistry. J Clin Virol. 2004;31:275‑82.

https://doi.org/10.1016/j.jcv.2004.05.016

Murphy EL, Lee T-H, Chafets D, Nass CC, Wang B, Loughlin K,

et al. Higher human T lymphotropic virus (HTLV) provirus load is

associated with HTLV-I versus HTLV-II, with HTLV-II subtype A

versus B, and with male sex and a history of blood transfusion.

J Infect Dis. 2004;190:504-10. https://doi.org/10.1086/422398

Montanheiro PA, Oliveira AC, Posada-Vergara MP, Milagres AC,

Tauil C, Marchiori PE, et al. Human T-cell lymphotropic virus

type I (HTLV-I) proviral DNA viral load among asymptomatic

patients and patients with HTLV-II-associated myelopathy/tropical

spastic paraparesis. Braz J Med Biol Res. 2005;28:1643‑7.https://doi.org/10.1590/S0100-879X2005001100011

Olindo S, Lézin A, Cabre P, Merle H, Saint-Vil M, Kaptue ME, et al.

HTLV-1 proviral load in peripheral blood mononuclear cells quantifie d

in 100 HAM/TSP patients: A marker of disease progression. J Neurol

Sci. 2005;237:53-9. https://doi.org/10.1016/j.jns.2005.05.010

Yakova M, Lézin A, Dantin F, Lagathu G, Olindo S, Jean‑Baptiste

G, et al. Increased proviral load in HTLV-1-infected patientswith rheumatoid arthritis or connective tissue disease.Retrovirol. 2005,2:4. https://doi.org/10.1186/1742-4690-2-4

Best I, Adaui V, Verdonck K, González E, Tipismana M, Clark D,

et al. Proviral load and immune markers associated with human

T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/

tropical spastic paraparesis (HAM/TSP) in Peru. Clin Exp

Immunol. 2006;146(2):226-33. doi: 10.1111/j.1365‑2249.20

03208.x https://pubmed.ncbi.nlm.nih.gov/19213697/

Tamegão-Lopes BP, Rezende PR, Maradei-Pereira LMC, Lemos

JAR. HTLV-1 and HTLV-2 proviral load: a simple method using

quantitative real time PCR. Rev Soc Bras Med Tropical S Paulo.

;39(6):548-52. https://www.scielo.br/pdf/rsbmt/v39n6/07.pdf

Vitone F, Gibellini D, Schiavone P, D’Antuono A, Gianni L,

Bon I, et al. Human T-lymphotropic virus type 1 (HTLV-1)

prevalence and quantitative detection of DNA proviral load

in individuals with indeterminate/positive serological results.

BMC Infect Dis. 2006;6:41. doi:10.1186/1471-2334-6-41.

Arruda BC, Lira RA, Loureiro P, Brandão L, Souza P, Souza WV,

et al. Evaluation of real time PCR technique to diagnosis of human

T-lymphotropic virus type I (HTLV-I) in patients in the Hematologia

da Fundação Hemope Hospital, in Northeastern Brazil. Rev Bras

Hematol Hemoter. 2008;30(5):384-9. https://www.scielo.br/j/

rbhh/a/6HJQDg8PQHVMBDPKg8ffP3M/?format=pdf&lang=en

Besson G, Kazanji M. One-step, multiplex, real-time PCR assay

with molecular beacon probes for simultaneous detection,

differentiation and quantification of human T-cell leukaemia

viruses types 1, 2 and 3. J Clin Microbiol. 2009;47(4):1129-35. doi:

1128/JCM.02006-08 https://jcm.asm.org/content/47/4/1129

Primo PJ, Siqueira I, Nascimento MCF, Oliveira MF, Farre L,

Carvalho EM, et al. High HTLV-1 proviral load, a marker for

HTLV-1-associated myelopathy/tropical spastic paraparesis, is

also detected in patients with infective dermatitis associated with

HTLV-1. Braz J Med Biol Res. 2009;42(8):761-4. https://www.scielo.

br/j/bjmbr/a/6CsgkdrvPpBk93Y7PZ9rXSc/?lang=en&format=pdf

Neto WK, Da-Costa AC, de Oliveira ACS, Martinez VP, Nukui

Y, Sabino EC, et al. Correlation between LTR point mutations

and proviral load levels among Human T cell Lymphotropic

Virus type 1 (HTLV-1) asymptomatic carriers. Virol J.

;8:535. http://www.virologyj.com/content/8/1/535

Waters A, Oliveira ALA, Coughlan S, de Venecia C, Schor D,

Leite A-C, Araújo AQC, et al. Multiplex real-time PCR for the

detection and quantitation of HTLV-1 and HTLV-2 proviral load:

addressing the issue of indeterminate HTLV results. J Clin Virol.

;52(1):38-44. https://doi.org/10.1016/j.jcv.2011.05.022

Cabral F, Arrudac LB, Araújo ML, Montanheiro P, Smid J,

Oliveira ACP, et al. Detection of human T-cell lymphotropic

virus type 1 in plasma samples. Vir Res. 2012;163:

-90. https://doi.org/10.1016/j.virusres.2011.08.014

Olavarria VN, Gomes AN, Kruschewsky RA, Bernardo

Galvão-Castro B, Grassi MFR. Evolution of HTLV-1 proviral

load in patients from Salvador, Brazil. Braz J Infect Dis.

;16(4):357-60. https://doi.org/10.1016/j.bjid.2012.06.022

Ribeiro MA, MD, Martins ML, Teixeira C, Ladeira R, Oliveira

MF, Januário JH, et al. Blocking vertical transmission of

human T cell lymphotropic virus type 1 and 2 through

breastfeeding interruption. Pediatr Infect Dis J. 2012;

:1139-43. doi: 10.1097/INF.0b013e318263215e.

Souza VG, Martins ML, Carneiro-Proietti ABF, Januário JN,

Ladeira RVP, Silva CMS, et al. High prevalence of HTLV‑1

and 2 viruses in pregnant women in São Luis, State of

Maranhão, Brazil. Rev Soc Bras Med Trop. 2012; 45(2):159‑62.

https://doi.org/10.1590/S0037-86822012000200004

Castro GM, Balangero MC, Maturano E, Mangeaud A,

Gallego SV. Development and validation of a real-time

PCR assay for a novel HTLV-1 tax sequence detection and

proviral load quantitation. J Virol Methods 2013;189:383‑7.

http://dx.doi.org/10.1016/j.jviromet.2013.02.018

Abad-Fernández M, Cabrera C, García E, Vallejo A. Transient

increment of HTLV-2 proviral load in HIV-1-co-infected patients

during treatment intensification with raltegravir. J Clin Virol.

;59:204-7. http://dx.doi.org/10.1016/j.jcv.2013.12.010

Ishihara K, Inokuchi N, Tsushima Y, Tsuruda K, Morinaga

Y, Hasegawa H, et al. Relevance of molecular tests for

HTLV-1 infection as confirmatory tests after the first

sero‑screening. J Immunoassay Immunoch. 2014;35(1):74‑82.

https://doi.org/10.1080/15321819.2013.792832

Cánepa C, Salido J, Ruggieri M, Fraile S, Pataccini G, Berini C,

Biglione M. Low proviral load is associated with indeterminate

Western Blot patterns in human T-cell lymphotropic virus type

infected individuals: could punctual mutations be related?

Viruses. 2015;7(11):5643-58. https://doi.org/10.3390/v7112897

Nasir IA, Ahmad AE, Emeribe AU, Shehu MS, Medugu JT,

Babayo A. Molecular detection and clinical implications of HTLV‑1

infections among antiretroviral therapy-naïve HIV-1‑infected

individuals in Abuja, Nigeria. Virology: Research and Treatment

;6:17-23. https://doi.org/10.4137/VRT.S35331

Vet JAM, Majithia AR, Marras SAE, Tyagi S, Dube S,

Poiesz BJ, et al. Multiplex detection of four pathogenic

retroviruses using molecular beacons Proc Natl Acad Sci USA.

;96(11):6394-9. https://doi.org/10.1073/pnas.96.11.6394

Dehée A, Césaire R, Desiré N, Lézin A, Bourdonné O, Béra

O, et al. Quantification of HTLV-1 proviral load by TaqMan

real-time PCR assay. J Virol Methods 2002;102:37-51.

https://doi.org/10.1016/S0166-0934(01)00445-1

Moens B, López G, Adaui V, González E, Kerremans L, Clark D,

et al. Development and validation of a multiplex real-time PCR

assay for simultaneous genotyping and human T-lymphotropic

virus type 1, 2, and 3 proviral load determination. J Clin

Microbiol. 2009;47(11):3682-91. doi: 10.1128/JCM.00781-09

Andrade RG, Ribeiro MA, Namen-Lopes MSS, Silva SMN,

Basques FV, Ribas JG, et al. Evaluation of the use of

real‑time PCR for human T cell lymphotropic virus 1 and 2 as

a confirmatory test in screening for blood donors. Rev Soc

Bras Med Trop. 2010;43(2):111-5. https://www.scielo.br/j/

rsbmt/a/6rTQ9jMdYwhGMkYL7vTVpzK/?format=pdf&lang=e

Furtado MSBS, Andrade RG, Romanelli LCF, Ribeiro MA, Ribas

JG, Torres EB. Monitoring the HTLV-1 proviral load in the peripheral

blood of asymptomatic carriers and patients with HTLV-associated

myelopathy/tropical spastic paraparesis from a Brazilian cohort:

ROC curve analysis to establish the threshold for risk disease.

J Med Virol. 2012; 84:664-71. doi: 10.1002/jmv.23227

Rosadas C, Cabral-Castro MJ, Vicente ACP, Peralta JM,

Puccioni-Sohler M. Validation of a quantitative real-time

PCR assay for HTLV-1 proviral load in peripheral blood

mononuclear cells. J Virol Methods 2013;193:536-41.

https://doi.org/10.1016/j.jviromet.2013.07.040

Kamihira S, Yamano Y, Iwanaga M, Sasaki D, Satake M, Okayama

A, et al. Intra- and inter-laboratory variability in human T-cell

leukemia virus type-1 proviral load quantification using real-ti me

polymerase chain reaction assays: A multi-center study. Cancer Sci.

;101:2361-7. https://doi.org/10.1111/j.1349-7006.2010.01720.x

Kuramitsu M, Okuma K, Nakashima M, Sato T, Sazaki D,

Hasegawa H, et al. Development of reference material

with assigned value for human T-cell leucemia virus

type 1 quantitaive PCR in Japan. Microbiol Immunol.

;62:673-6. https://doi.org/10.1111/1348-0421.12644

Gonçalves MG. Padronização e validação da PCR em tempo real

para a detecção rápida e quantificação de carga proviral de HTL V-1

e HTLV-2. Tese (Doutorado em Ciências) - Secretaria de Estado da

Saúde de São Paulo, Programa de Pós-Graduação em Ciências da

Coordenadoria de Controle de Doenças, São Paulo, 2019; 158p.

https://pesquisa.bvsalud.org/ses/resource/pt/biblio-1051598

Bandeira LM, Puga MAM, de Paula VS, Demarchi LHF, Lichs

GGC, Domingos JA, et al. Use of synthetic oligonucleotides

for determination of HTLV-1 proviral load by real-time PCR:

a helpful alternative approach in the clinical management. J

Appl Microbiol. 2020;129:768-74. doi:10.1111/jam.14646

Brunetto GS, Massoud R, Leibovitch EC, Caruso B, Johnson

K, Ohayon J, et al. Digital droplet PCR (ddPCR) for the precise

quantification of human T-lymphotropic virus 1 proviral loads in

peripheral blood and cerebrospinal fluid of HAM/TSP patients and

identification of viral mutations. J Neurovirol. 2014;20(4):341- 51.

https://link.springer.com/article/10.1007/s13365-014-0249-3

Hedberg ST, Eriksson L, Demontis MA, Mölling P, Sundqvist M,

Taylor G, et al. Droplet digital PCR for absolute quantification

of proviral load of human T-cell lymphotropic virus

(HTLV) types 1 and 2. J Virol Methods. 2018; 60:70‑4.

https://doi.org/10.1016/j.jviromet.2018.07.003

Yurick D, Khoury G, Clememns B, Loh L, Pham H,

Kedzierska K, et al. Multiplex droplet digital PCR assay for

quantification of human T-cell leukemia virus type 1 subtype

c DNA proviral load and T cells from blood and respiratory

exudates sampled in a remote setting. J Clin Microbiol.

;57(2):e01063-18. https://doi.org/10.1128/JCM.01063-18

Gomes YCP. Determinação da acurácia do teste de amplificação

isotérmica de ácidos nucleicos mediada por alça (LAMP) para a

confirmação de infecção pelos vírus linfotrópicos para células t

humanas dos tipos 1 e 2 (HTLV-1/2). Dissertação (Mestrado emCiências) – Fundação Oswaldo Cruz, Programa de Pós-Graduação emPesquisa Clínica em Doenças Infecciosas, Rio de Janeiro, 2020; 72p.

Gomes Y, Caterino-de-Araujo A, Campos K, Gonçalves MG, Leite

AC, Lima MA, et al. Loop-Mediated Isothermal Amplification (LAMP)

Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2

Infection. Viruses 2020;12:981 https://doi.org/10.3390/v12090981

De Giorgi V, Zhou H, Alter HJ, Allison RD. A microarray‑based

pathogen chip for simultaneous molecular detection of

transfusion–transmitted infectious agents. J Transl Med.

;17:156 https://doi.org/10.1186/s12967-019-1905-4

Norouzi M, Ghobadi MZ, Golmimi M, Mozhgani SH, Ghourchian H,

Rezaee SA. Quantum dot-based biosensor for the detection of human

T-lymphotropic virus-1. Analitycal Letters. 2017;50(15):2402‑11.

http://dx.doi.org/10.1080/00032719.2017.1287714

Fani M, Rezayi M, Pourianfar HR, Meshkat Z, Makvandi

M, Gholami M, et al. Rapid and label-free electrochemical

DNA biosensor based on a facile one-step electrochemical

synthesis of rGO–PPy–(L-Cys)–AuNPs nanocomposite for the

HTLV-1 oligonucleotide detection. Biotechnology and Applied

Biochemistry June 2020. https://doi.org/10.1002/bab.1973

Becherer L , Hess JF, Frischmann S, Bakheit M, Nitschko

H, Stinco S, et al. Point-of-care system for HTLV-1 proviral

load quantification by digital mediator displacement LAMP.

Micromachines. 2021;12:159. https://doi.org/10.3390/mi12020159

Machuca A, Soriano V. In vivo fluctuation of HTLV-I and

HTLV-II proviral load in patients receiving antiretroviral

drugs. J Acquir Immune Defic Syndr. 2000;24(2):189-93.

https://doi.org/10.1097/00126334-200006010-00017

Tamiya S, Matsuoka M, Etoh K-I, Watanabe T, Kamihira S,

Yamaguchi K, et al. Two types of defective human T-lymphotropic

virus type I provirus in Adult T-cell Leukemia. Blood 1996;88:3065-73.

https://doi.org/10.1182/blood.V88.8.3065.bloodjournal8883065

Ramirez E, Fernandez J, Cartier L, Villota C, Rios M. Defective

human T-cell lymphotropic virus type I (HTLV-I)

provirus in seronegative tropical spastic paraparesis/

HTLV‑I‑associated myelopathy (TSP/HAM) patients. Vir Res.

;91:231-9. doi: 10.1016/s0168-1702(02)00276-9

Miyazaki M, Yasunaga J-I, Taniguchi Y, Tamiya S, Nakahata T,

Matsuoka M. Preferential selection of human T-cell leukemia

virus type 1 provirus lacking the 5’ long terminal repeat during

oncogenesis. J Virol. 2007;81:5714-23. doi: 10.1128/JVI.02511-06

Takenouchi H, Umeki K, Sasaki D, Yamamoto I, Nomura

H, Takajo I, et al. Defective human T-lymphotropic virus

type 1 provirus in asymptomatic carriers. Int J Cancer.

;128:1335-43. https://doi.org/10.1002/ijc.25450

Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T,

Umeki K, et al. Proviral features of human T cell leukemia virus

type 1 in carriers with indeterminate Western blot analysis results.

J Clin Microbiol. 2017;55:2838-49. doi: 10.1128/JCM.00659-17

Hashikura Y, Umeki K, Umekita K, Nomura H, Yamada A, Yamamoto

I, et al. Infection of defective human T-lymphotropic virus type 1.

Hum Cell. 2017;30(2):117-23. doi: 10.1007/s13577-016-0156-4.

Katsuya H, Islam S, Tan BJY, Ito J, Miyazato P, Matsuo M, , Inada

Y, et al. The nature of the HTLV-1 provirus in naturally infected

individuals analyzed by the viral DNA-capture-seq approach. Cell

Reports. 2019;29:724-35. doi: 10.1016/j.celrep.2019.09.016

Campos KR, Caterino-de-Araujo A. Provirus Mutations of

Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV‑2)

in HIV-1-Coinfected Individuals. mSphere. 2020 Sep

;5(5):e00923-20. https://doi.org/10.1128/mSphere.00923-20116. Blanco S, Frutos MC, Balangero MC, Gallego SV. HumanT-lymphotropic virus type 1 infection in absence of tax gene: Achallenge for molecular diagnosis. Infection, Genetics and Evolution2021;90:104765 https://doi.org/10.1016/j.meegid.2021.104765

Caterino-de-Araujo A, Campos KR. Defective particles of

human T-lymphotropic virus and negative results in molecular

assays. Infection, Genetics and Evolution 2021; (submitted)

Castro-Costa CM, Carton H, Santos TJT. HTLV-I negative

tropical sapastic paraparesis. A scientific challenge.

Arq Neuropsiquiatr. 2001;59(2-A):289-94. https://doi.

org/10.1590/S0004-282X2001000200031

Segurado ACC, Biasutti C, Zeigler R, Rodrigues C, Damas

CD, Jorge MLSG, et al. Identification of human T-lymphotropic

virus type I (HTLV-I) subtypes using restricted fragment length

polymorphism in a cohort of asymptomatic carriers and patients

with HTLV-I associated myelopathy/tropical spastic paraparesis

from São Paulo, Brazil. Mem Inst Oswaldo Cruz. 2002;97:329‑33.

https://doi.org/10.1590/S0074-02762002000300009

Colin DD, Alcântara LCJ, Santos FLN, Uchôa R, Tavares-Neto J.

Seroprevalence of human T cell lymphotropic virus infection and

associated factors of risk in blood donors of Rio Branco city, AC,

Brazil (1998-2001). Rev Soc Bras Med Trop. 2003;36(6):677‑83.

https://doi.org/10.1590/S0037-86822003000600006

Santos TJT, Costa CMC, Goubau P, Vandamme AM, Desmyter J,

Dooren SV, et al. Western blot seroindeterminate individuals for

human T-lymphotropic virus 1/2 (HTLV-1/2) in Fortaleza (Brazil):

a serological and molecular diagnostic and epidemiological

approach. Braz J Infect Dis. 2003;7(3):202-9.https://www.scielo.

br/j/bjid/a/rtbTvFnxS8dhwhtDS7bWDzr/?lang=en&format=pdf

Kashima S, Alcantara LC, Takayanagui OM, Cunha MAV,

Galvao‑Castro B, Pombo-de-Oliveira MS, et al. Distribution of human

T cell lymphotropic virus type 1 (HTLV-1) subtypes in Brazil: genetic

characterization of LTR and tax region. AIDS Res Hum Retroviruses

;22(10):953‑9. https://doi.org/10.1089/aid.2006.22.953

Pimenta FCF, Haddad SK, Medeiros Filho JG, Costa MJC,

Diniz MFM, Fernandes MP, et al. Prevalence ratio of HTLV-1

in nursing mothers from the state of Paraíba,

Northeastern Brazil. J Hum Lact. 2008;24(3):289-92.

https://doi.org/10.1177/0890334408316084

Dal Fabbro MMFJ, Cunha RV, Bóia MN, Portela P, Botelho CA,

Freitas GMB, et al. Infecção pelo HTLV 1/2: atuação no pré-natal

como estratégia de controle da doença no Estado de Mato

Grosso do Sul. Rev Soc Bras Med Trop. 2008; 41(2):148‑51.

https://doi.org/10.1590/S0037-86822008000200003

Nascimento LB, Carneiro MAS, Teles SA, Lopes CLR,

Reis NRS, Costa e Silva AM, et al. Prevalence of infection

due to HTLV-1 in remnant quilombos in Central Brazil.

Rev Soc Bras Med Trop. 2009;42(6):657-60.

https://doi.org/10.1590/S0037-86822009000600009

Martins ML, Santos AC, Namen-Lopes MS, Barbosa-Stancioli

EF,Utsch DG, Carneiro-Proietti AB. Long-term serological follow

up of blood donors with an HTLV-indeterminate western blot:

antibody profile of seroconverters and individuals with falsereactions. J Med Virol. 2010; 82:1746-53. doi: 10.1002/jmv.21881

Galetto LR, Lunge VR, Béria JU, Tietzmann DC, Stein AT,

Simon D. Prevalence and risk factors for human T

cell lymphotropic virus infection in Southern Brazilian

HIV-positive patients. AIDS Res Hum Retroviruses

;30(9):907‑11. https://doi.org/10.1089/aid.2013.0210

Martin F, Tagaya Y, Gallo R. Time to eradicate

HTLV-1: an open letter to WHO. Lancet. 2018;391:

–1894. doi:10.1016/S0140-6736(18)30974-7

International Retrovirology Association (IRVA). [Internet].

[Acesso em 11 jun 2021]. Disponível em: https://htlv.net/

Caterino-de-Araujo A. Dia Mundial do HTLV - 10 de Novembro. Rev.

Inst. Adolfo Lutz, 2018; 77:e1751. http://www.ial.sp.gov.br/resources/

insituto-adolfo-lutz/publicacoes/rial/10/rial77_completa/1751.pdf

HTLV Channel. 2020 [Internet, Youtube]. [Acesso

em 11 jun 2021] Disponível em: https://www.youtube.

com/channel/UCI6aLSTtk7chXMeybJ92Fhw

Ministério da Saúde (MS). Secretaria de Vigilância em

Saúde. Departamento de Doenças de Condições Crônicas

e Infecções Sexualmente Transmissíveis. Protocolo

Clínico e Diretrizes Terapêuticas para Atenção Integral

às Pessoas com Infecções Sexualmente Transmissíveis

(IST). 1ª edição. Brasília: MS; 2020. 248p.

Rosadas C, Brites C, Arakaki-Sanchez D, Casseb J, Ishak

R. Brazilian Protocol for Sexually Transmitted Infections

: human T-cell lymphotropic virus (HTLV) infection.

Rev Soc Bras Med Trop. 2021;54(Suppl I): e2020605

https://doi.org/10.1590/0037-8682-605-2020

I WebSimpósio de HTLV - PCDT do HTLV: 2020 - Desafios e

Perspectivas - Parte 1 [Internet]. Diagnóstico Laboratorial. [Acesso em

nov 2020]. Disponível em: https://www.youtube.com/watch?v=cd

BeUrNmnE8&list=PLcprvSVJObvc6ij_-Ep3eLJPpPITfy0xN&index=2

Episódio 24 - Diagnóstico da Infecção de HTLV: Histórico e

Desafios 2021. [Internet]. [Acesso em 20 abr 2021]. Disponível

em: https://www.youtube.com/watch?v=r2mpMuNmH6A

Word Health Organization (WHO). Human T-lymphotropic

virus type 1: technical report. Geneva: WHO; 2021. 78p.

https://www.who.int/publications/i/item/9789240020221

Creative Commons License
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.

Copyright (c) 2022 Adele Caterino-de-Araujo, Maria Gisele Gonçalves

Downloads

Não há dados estatísticos.

Métricas

Carregando Métricas ...