Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals

被引:8
作者
Campos, Karoline Rodrigues [1 ]
Caterino-de-Araujo, Adele [1 ]
机构
[1] Adolfo Lutz Inst, Coordenadoria Controle Doencas, Secretaria Estado Saude, Lab Pesquisa HTLV,Ctr Imunol, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
human T-lymphotropic virus 1; HTLV-1; human T-lymphotropic virus 2; HTLV-2; HIV; coinfection; provirus mutation; sequencing; diagnostic impairment; CELL LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; I-ASSOCIATED MYELOPATHY; TYPE-1; HTLV-1; SAO-PAULO; MOLECULAR CHARACTERIZATION; HIV; RETROVIRUS; ANTIBODIES; BRAZIL;
D O I
10.1128/mSphere.00923-20
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Provirus mutations of human T-lymphotropic virus 1 (HTLV-1), mostly the lack of the 5' long terminal repeat (LTR) genomic region, have been described and associated with severe adult T cell leukemia/lymphoma (ATLL), non-sense point mutations with low proviral load, and Western blotting indeterminate results. Until now, no information concerning provirus mutations of HTLV-2 and its consequences, as well as those of HTLV-1/2 in HIV-coinfected individuals, had been described. Therefore, we searched for these mutations in provirus samples of 44 HIV/HTLV-1-and 25 HIV/HTLV-2-coinfected individuals. Using protocols well established for amplification and sequencing of segments of the LTR, env, and tax regions, we searched for defective type 1 particles that retain LTR5 and lack internal sequences and type 2 particles that lack the 5'LTR region. In addition, using as references the prototypes ATK (HTLV-1) and Mo (HTLV-2), we searched for point mutations in the LTR and synonyms and non-synonymous mutations and non-sense mutations in env and tax regions. Defective HTLV-1 and HTLV-2 provirus type 1 or 2 was detected in 31.8% of HIV/HTLV-1- and 32.0% of HIV/HTLV-2-coinfected individuals. Synonymous and nonsynonymous mutations were identified mostly in HTLV-2 and associated with lower levels of specific antibodies. No non-sense mutations that resulted in premature termination of Env and Tax proteins were detected. On the contrary, mutation in the stop codon of Tax2a produced a long protein characteristic of the HTLV-2c subtype. The clinical significance of these mutations in coinfected individuals remains to be defined, but they confirmed the lower sensitivity of serological and molecular diagnostic tests in HIV/HTLV-1/2 coinfections. IMPORTANCE HTLV-1 and HTLV-2 are endemic to Brazil, and they have different effects in HIV/AIDS disease progression. HIV/HTLV-1 has been described as accelerating the progression to AIDS and death, while HIV/HTLV-2 slows the progression to AIDS. Provirus mutations of HTLV-1 were implicated in severe leukemia development and in problems in the diagnosis of HTLV-1; in contrast, provirus mutations of HTLV-2 had not been confirmed and associated with problems in HTLV-2 diagnosis or disease outcome. Nevertheless, data obtained here allowed us to recognize and understand the false-negative results in serologic and molecular tests applied for HTLV-1 and HTLV-2 diagnosis. Defective proviruses, as well as synonymous and non-synonymous mutations, were associated with the diagnosis deficiencies. Additionally, since HIV-1 and HTLV-1 infect the same cells (CD4 positive), the production of HIV-1 pseudotypes with HTLV-1 envelope glycoprotein during HIV/HTLV-1 coinfection cannot be excluded. Defective provirus of HTLV-2 and Tax2c is speculated to influence progression to AIDS.
引用
收藏
页数:16
相关论文
共 56 条
[1]   ISOLATION OF A T-LYMPHOTROPIC RETROVIRUS FROM A PATIENT AT RISK FOR ACQUIRED IMMUNE-DEFICIENCY SYNDROME (AIDS) [J].
BARRESINOUSSI, F ;
CHERMANN, JC ;
REY, F ;
NUGEYRE, MT ;
CHAMARET, S ;
GRUEST, J ;
DAUGUET, C ;
AXLERBLIN, C ;
VEZINETBRUN, F ;
ROUZIOUX, C ;
ROZENBAUM, W ;
MONTAGNIER, L .
SCIENCE, 1983, 220 (4599) :868-871
[2]  
Barreto FK, 2014, AIDS RES HUM RETROV, V30, P92, DOI [10.1089/aid.2013.0181, 10.1089/AID.2013.0181]
[3]  
BARTHOLOMEW C, 1987, LANCET, V2, P1469
[4]  
Beilke MA, 2012, AIDS RES HUM RETROV, V28, P139, DOI [10.1089/AID.2011.0342, 10.1089/aid.2011.0342]
[5]   Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences [J].
Bertazzoni, Umberto ;
Turci, Marco ;
Avesani, Francesca ;
Di Gennaro, Gianfranco ;
Bidoia, Carlo ;
Romanelli, Maria Grazia .
VIRUSES-BASEL, 2011, 3 (05) :541-560
[6]   Co-infection with HTLV-1 is associated with a shorter survival time for HIV-1-infected patients in Bahia, Brazil [J].
Brites, C ;
Alencar, R ;
Gusmao, R ;
Pedroso, C ;
Netto, EM ;
Pedral-Sampaio, D ;
Badaró, R .
AIDS, 2001, 15 (15) :2053-2055
[7]  
Brites C, 2009, AIDS REV, V11, P8
[8]   A PATHOGENIC RETROVIRUS (HTLV-III) LINKED TO AIDS [J].
BRODER, S ;
GALLO, RC .
NEW ENGLAND JOURNAL OF MEDICINE, 1984, 311 (20) :1292-1297
[9]   Comparative performances of serologic and molecular assays for detecting human T lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) in patients infected with human immunodeficiency virus type 1 (HIV-1) [J].
Campos, Karoline Rodrigues ;
Goncalves, Maria Gisele ;
Costa, Nadia Aparecida ;
Caterino-de-Araujo, Adele .
BRAZILIAN JOURNAL OF INFECTIOUS DISEASES, 2017, 21 (03) :297-305
[10]   Multiple recombinant events in human T-cell Leukemia virus Type 1: complete sequences of recombinant African strains [J].
Cassar, Olivier ;
Desrames, Alexandra ;
Marcais, Ambroise ;
Gout, Olivier ;
Taylor, Graham P. ;
Hermine, Olivier ;
Soriano, Vicente ;
de Mendoza, Carmen ;
Dehan, Oceane ;
Le Mener, Margot ;
Afonso, Philippe, V ;
Gessain, Antoine .
EMERGING MICROBES & INFECTIONS, 2020, 9 (01) :913-923