Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals
| العنوان: | Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals |
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| المؤلفون: | Adele Caterino-de-Araujo, Karoline Rodrigues Campos |
| المصدر: | mSphere, Vol 5, Iss 5 (2020) mSphere |
| بيانات النشر: | American Society for Microbiology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Nonsynonymous substitution, Molecular Biology and Physiology, Adolescent, viruses, 030106 microbiology, diagnostic impairment, HIV Infections, medicine.disease_cause, Microbiology, Virus, Young Adult, 03 medical and health sciences, Proviruses, immune system diseases, hemic and lymphatic diseases, medicine, Humans, Point Mutation, Molecular Biology, Aged, human T-lymphotropic virus 1, Mutation, biology, Point mutation, provirus mutation, human T-lymphotropic virus 2, HIV, virus diseases, sequencing, Middle Aged, Provirus, medicine.disease, biology.organism_classification, HTLV-I Infections, Virology, coinfection, QR1-502, 030104 developmental biology, HTLV-2, HTLV-1, Human T-lymphotropic virus 1, Human T-lymphotropic virus 2, Coinfection, Female, Brazil, Research Article |
| الوصف: | 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 nonsynonymous 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. 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 LTRs 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 nonsynonymous 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 nonsynonymous 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. |
| تدمد: | 2379-5042 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::23aa851ad660f78eb11b8b47cb9eee91Test https://doi.org/10.1128/msphere.00923-20Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....23aa851ad660f78eb11b8b47cb9eee91 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23795042 |
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