In vivo analysis of replication and immunogenicity of proviral clones of human T-lymphotropic virus type 1 with selective envelope surface-unit mutations.
نویسندگان
چکیده
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell lymphoma/leukemia (ATL). The HTLV-1 envelope gene exhibits limited variability when examined from infected individuals, but has not been tested using infectious clones of the virus in animal models. In vitro assays indicate that HTLV-1 envelope (Env) Ser75Ile, Asn95Asp, and Asn195Asp surface unit (SU) mutants are able to replicate in and immortalize lymphocytes. Herein, we examined the effects of these Env mutants in rabbits inoculated with HTLV-1 immortalized ACH.75, ACH.95, or ACH.195 cell lines (expressing full-length molecular clones with the SU mutations) or the ACH.1 cell line (expressing wild-type SU). All rabbits became infected, and the fidelity of the mutations was maintained throughout the 8-week study. However, SU point mutations resulted in decreased antibody responses to viral group-associated antigen (Gag) and Env antigens. ACH.195 rabbits had a selective decreased antibody response to SU, and one ACH.195 rabbit had an antibody response to both HTLV-1 and HTLV-2 SUs. Some mutant inoculation groups had altered proviral loads. However, peripheral-blood mononuclear cell (PBMC) proviral loads did not correlate with antibody responses. Our data are the first to demonstrate that mutations in critical determinants of HTLV-1 Env SU altered antibody responses and proviral loads, but do not prevent viral replication in vivo.
منابع مشابه
Human T-lymphotropic Virus Type I (HTLV-I) Proviral Load and Clinical Features in Iranian HAM/TSP Patients
متن کامل
P178: Can Human T-Lymphotropic Virus Proviral Load Predict the Severity of Clinical Features in HAM/TSP Patients?
HTLV-1 is the causative agent for a neurologic disease named HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP). Paraparesis of the lower limbs which appears gradually is the most common clinical feature of this disease. The indirect involvement of the nervous system by lymphocytes is more probable than the direct attack of the virus to the neurons. The proviral load (PVL) is ...
متن کاملHigh proviral load of human T cell lymphotropic virus type-1 facilitates coronary artery diseases
Objective(s): Coronary artery disease (CAD) is known as a life threatening disease, worldwide. In this study the role of HTLV-1 infection was evaluated on cardiac involvement in an endemic region of northeastern Iran.Materials and Methods: Serologic and molecular tests for HTLV-1 infection were carried out in subjects who had coronary an...
متن کاملDengue virus type-3 envelope protein domain III; expression and immunogenicity
Objective(s): Production of a recombinant and immunogenic antigen using dengue virus type-3 envelope protein is a key point in dengue vaccine development and diagnostic researches. The goals of this study were providing a recombinant protein from dengue virus type-3 envelope protein and evaluation of its immunogenicity in mice. Materials and Methods: Multiple amino acid sequences of different i...
متن کاملDeep Sequencing Analysis of Human T Cell Lymphotropic Virus Type 1 Long Terminal Repeat 5' Region from Patients with Tropical Spastic Paraparesis/Human T Cell Lymphotropic Virus Type 1-Associated Myelopathy and Asymptomatic Carriers.
The aim of this study was to analyze patients by deep sequencing the human T cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR) region in order to determine if minor and/or major mutations in this promoter region might be associated with tropical spastic paraparesis (TSP)/human T cell lymphotropic virus type 1-associated myelopathy (HAM) outcome or proviral load or HTLV-1 expres...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 106 10 شماره
صفحات -
تاریخ انتشار 2005