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Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.

ABSTRACT: BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HTLV-1 infected donor, is reported. The recipients were treated with two HTLV-1 enzyme inhibitors 3 weeks post exposure following the detection of HTLV-1 provirus at low level in each recipient. HTLV-1 infection was serially monitored by serology, quantification of proviral load and HTLV-1 2LTR DNA circles and by HTLV-1 unique integration site analysis. RESULTS:HTLV-1 antibodies were first detected 16-39 days post-transplantation. HTLV-1 provirus was detected by PCR on day 16-23 and increased by 2-3 log by day 38-45 with a peak proviral doubling time of 1.4 days, after which steady state was reached. The rapid proviral load expansion was associated with high frequency of HTLV-1 2LTR DNA circles. The number of HTLV-1 unique integration sites was high compared with established HTLV-1 infection. Clonal expansion of infected cells was detected as early as day 37 with high initial oligoclonality index, consistent with early mitotic proliferation. CONCLUSIONS:In recipients infected through organ transplantation HTLV-1 disseminated rapidly despite early anti-HTLV-1 treatment. Proviral load set point was reached within 6 weeks. Seroconversion was not delayed. Unique integration site analysis and HTLV-1 2LTR DNA circles indicated early clonal expansion and high rate of infectious spread.

SUBMITTER: Cook LB

PROVIDER: S-EPMC4706667 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.

Cook Lucy B M LB Melamed Anat A Demontis Maria Antonietta MA Laydon Daniel J DJ Fox James M JM Tosswill Jennifer H C JH de Freitas Declan D Price Ashley D AD Medcalf James F JF Martin Fabiola F Neuberger James M JM Bangham Charles R M CR Taylor Graham P GP

Retrovirology 20160108

<h4>Background</h4>Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HT ...[more]

PMID: 26745892

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Project description:Interventions: Brief name: anal swab Kidney transplant recipients attending routine review appointments will be approached to participate. They will be provided a participant information and consent form (PICF) detailing the purpose, methods and risks and benefits of the study. The study will include adults willing and able to give informed consent in English. Consented participants will complete an initial coded demographic and behavioural questionnaire. Trained staff will then take an anal swab taken using a moistened Dacron swab for subsequent HPV testing. The Dacron swab will be vigorously eluded into a ThinPrep (Hologic) vial containing PreservCyt fixative medium. Any participant with either a significant cytological abnormality, or in whom high risk HPV is detected, will be referred for further investigation at a specialist clinic. A letter will be sent to participants with negative or low-risk results as well as their nominated GP. This pilot study will evaluate the feasibility of collecting potentially sensitive behavioural data, taking anal swab specimens and performing rectal examinations, in order to identify those at high risk of serious disease. Primary outcome(s): Prevalence of type-specific anal human papilloma virus (HPV) infection in renal transplant recipients, using PCR amplification of target DNA, and hybridization with a reverse line blot system.[ Anal swab will be performed within 14 days after completion of baseline questionnaire. Genotyping will be performed in batches, for every 20 participant samples.];Prevalence and type of anal cytological abnormalities in renal transplant recipients, using ThinPrep (Hologic) standard procedure. [ Anal swab will be performed within 14 days after completion of baseline questionnaire. Cytology testing will be performed within 7 days of sample collection.];Feasibility of use of anal swabs as a screening tool for the detection of HPV infection and abnormal cytological abnormalities. This will be assessed through enrolment rates from all eligible approached participants and also feedback given in the baseline questionnaires.[ Feasibility will be assessed after all participants have been tested, and followed up if needed.] Study Design: Purpose: Diagnosis; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Efficacy

Dataset Information

Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.

Publications

Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.

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