The effect of antiretroviral therapy on HTLV infection

Machuca, Ana; Rodés, Berta; Soriano, Vincent

doi:10.1016/s0168-1702(01)00287-8

Cited by 44 publications

(26 citation statements)

References 30 publications

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“…A previous study reported that a reverse transcriptase inhibitor, lamivudine, reduced the proviral load in a patient with HAM/TSP (56), implicating internal contagion in maintaining the number of infected cells in vivo. However, another study reported that lamivudine had no definite effect on proviral load (34). In this study, administering tenofovir to block the spread of infection to new cells did not influence the proviral load in hu-PBMC-NOG mice, even though tenofovir has been reported to be more efficient in inhibiting HTLV-1 replication than lamivudine (20).…”

Section: Discussioncontrasting

confidence: 51%

De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common γ-Chain Knockout Mice

Miyazato¹,

Yasunaga²,

Taniguchi³

et al. 2006

J Virol

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Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a disease that is triggered after a long latency period. HTLV-1 is known to spread through cell-to-cell contact. In an attempt to study the events in early stages of HTLV-1 infection, we inoculated uninfected human peripheral blood mononuclear cells and the HTLV-1-producing cell line MT-2 into NOD-SCID, common ␥-chain knockout mice (human PBMC-NOG mice). HTLV-1 infection was confirmed with the detection of proviral DNA in recovered samples. Both CD4؉ and CD8 ؉ T cells were found to harbor the provirus, although the latter population harbored provirus to a lesser extent. Proviral loads increased with time, and inverse PCR analysis revealed the oligoclonal proliferation of infected cells. Although tax gene transcription was suppressed in human PBMC-NOG mice, it increased after in vitro culture. This is similar to the phenotype of HTLV-1-infected cells isolated from HTLV-1 carriers. Furthermore, the reverse transcriptase inhibitors azidothymidine and tenofovir blocked primary infection in human PBMC-NOG mice. However, when tenofovir was administered 1 week after infection, the proviral loads did not differ from those of untreated mice, indicating that after initial infection, clonal proliferation of infected cells was predominant over de novo infection of previously uninfected cells. In this study, we demonstrated that the human PBMC-NOG mouse model should be a useful tool in studying the early stages of primary HTLV-1 infection.

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Section: Discussioncontrasting

confidence: 51%

De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common γ-Chain Knockout Mice

Miyazato¹,

Yasunaga²,

Taniguchi³

et al. 2006

J Virol

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“…The length polymorphism generated by PCR amplification of the HTLV-1 flanking sequences was analyzed by the linear PCR amplification of both the 3Ј extremity of the provirus and its flanking sequence (runoff). Two microliters of the amplified product was submitted to 10 cycles of linear PCR with 2 M of primer BIO5 (5Ј-TGGCTCGGAGCCAGCGACAGCCCAT-3Ј; positions 8995 to 9020) radiolabeled with 32 P at the 5Ј end, 1 U of the Stoffel fragment of Taq DNA polymerase (Perkin-Elmer Applied Biosystems, Courtaboeuf, France), and 200 M of each deoxynucleoside triphosphate in a final volume of 20 l. The thermal cycling parameters were as follows: 95°C for 10 min and 10 cycles of 95°C for 60 s, 58°C for 60 s, and 72°C for 3 min, followed by a final elongation step of 10 min at 72°C. After the mixture was boiled, 2 l of the runoff products was analyzed on a 6% sequencing gel.…”

Section: Methodsmentioning

confidence: 99%

“…The median length of survival for patients with AIDS receiving modern treatment, i.e., triple therapy, is currently over 8 years; in contrast, the prognosis for HTLV-1-associated diseases remains extremely poor. To date, there is no effective treatment for TSP/HAM (32), while the median overall length of survival for patients with ATLL does not exceed a few months (3).…”

mentioning

confidence: 99%

Inhibitors of Strand Transfer That Prevent Integration and Inhibit Human T-Cell Leukemia Virus Type 1 Early Replication

Rabaaoui

Zouhiri²,

Lançon

et al. 2008

Antimicrob Agents Chemother

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The replication of the retrovirus human T-cell leukemia virus type 1 (HTLV-1) is linked to the development of lymphoid malignancies and inflammatory diseases. Data from in vitro, ex vivo, and in vivo studies have revealed that no specific treatment can prevent or block HTLV-1 replication and therefore that there is no therapy for the prevention and/or treatment of HTLV-1-associated diseases in infected individuals. HTLV-1 and human immunodeficiency virus type 1 (HIV-1) integrases, the enzymes that specifically catalyze the integration of these retroviruses in host cell DNA, share important structural properties, suggesting that compounds that inhibit HIV-1 integration could also inhibit HTLV-1 integration. We developed quantitative assays to test, in vitro and ex vivo, the efficiencies of styrylquinolines and diketo acids, the two main classes of HIV-1 integrase inhibitors. The compounds were tested in vitro in an HTLV-1 strand-transfer reaction and ex vivo by infection of fresh peripheral blood lymphocytes with lethally irradiated HTLV-1-positive cells. In vitro, four styrylquinoline compounds and two diketo acid compounds significantly inhibited HTLV-1 integration in a dose-dependent manner. All compounds active in vitro decreased cell proliferation ex vivo, although at low concentrations; they also dramatically decreased both normalized proviral loads and the number of integration events during experimental ex vivo primary infection. Accordingly, diketo acids and styrylquinolines are the first drugs that produce a specific negative effect on HTLV-1 replication in vitro and ex vivo, suggesting their potential efficiency for the prevention and treatment of HTLV-1-associated diseases.Human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) are exogenous retroviruses pathogenic for humans. Although both viruses are lymphotropic, their pathogenicities depend on strongly distinct mechanisms. Schematically, in vivo, HIV infection triggers the progressive elimination of CD4 ϩ lymphocytes, leading to immunosuppression, whereas HTLV-1 infection is associated with the clonal expansion of infected cells, possibly leading to malignant CD4 ϩ proliferation or to spinal cord infiltration, infection, and inflammation. Clinically, HIV-induced cellular defects are regularly linked to the development of AIDS, whereas in a minority of carriers, HTLV-1 infection causes adult T-cell leukemia/lymphoma (ATLL) and/or tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). The median length of survival for patients with AIDS receiving modern treatment, i.e., triple therapy, is currently over 8 years; in contrast, the prognosis for HTLV-1-associated diseases remains extremely poor. To date, there is no effective treatment for TSP/HAM (32), while the median overall length of survival for patients with ATLL does not exceed a few months (3).Integration of a DNA copy of the viral RNA genome into host cellular DNA is essential and unique to the retroviral life cycle. After completion of reverse...

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“…1 In clinical reports and murine experiments, the retrovirus HTLV-1 has been implicated as a causative agent of Sjö gren syndrome (SS). 2,3 Myelopathy is a recognized complication of primary SS, and it has been shown that it responds to immunosuppressive treatment.…”

Section: Arch Neurol 2006;63:1318-1320mentioning

confidence: 99%

Combined Antiviral-Immunosuppressive Treatment in Human T-Lymphotrophic Virus 1–Sjögren–Associated Myelopathy

Pot¹,

Chizzolini²,

Vokatch³

et al. 2006

Arch Neurol

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Background:In several studies, antiretroviral drugs (principally zidovudine) have been used with success in the treatment of myelopathy associated with human Tlymphotrophic virus 1 (HTLV-1) (tropical spastic paraparesis-HTLV-1-associated myelopathy). The retrovirus HTLV-1 has been implicated as a causative agent of Sjö gren syndrome (SS) in clinical reports and murine experiments. Moreover, a recognized complication of primary SS is a myelopathy, which has been shown in case reports to respond to immunosuppressive treatment.Objective: To describe a patient with a rapidly progressive, extensive myelopathy with evidence of HTLV-1 infection and SS (probably secondary to HTLV-1) in whom we achieved spectacular therapeutic success using combined immunosuppressive and antiviral therapy.

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The effect of antiretroviral therapy on HTLV infection

Cited by 44 publications

References 30 publications

De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common γ-Chain Knockout Mice

De Novo Human T-Cell Leukemia Virus Type 1 Infection of Human Lymphocytes in NOD-SCID, Common γ-Chain Knockout Mice

Inhibitors of Strand Transfer That Prevent Integration and Inhibit Human T-Cell Leukemia Virus Type 1 Early Replication

Combined Antiviral-Immunosuppressive Treatment in Human T-Lymphotrophic Virus 1–Sjögren–Associated Myelopathy

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