Retroviridae: Human T-Lymphotropic Virus-I (HTLV-I)/Adult T-CeU Leukemia Virus (ATLV)

Author(s):  
Naoki Yamamoto ◽  
Yorio Hinuma
2020 ◽  
Vol 11 ◽  
Author(s):  
Sepehr Aghajanian ◽  
Majid Teymoori-Rad ◽  
Ghazale Molaverdi ◽  
Sayed-Hamidreza Mozhgani

HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a neuropathological disorder in 1–3% of individuals infected with Human T-lymphotropic virus 1 (HTLV-1). This condition is characterized by progressive spastic lower limb weakness and paralysis, lower back pain, bladder incontinence, and mild sensory disturbances resembling spinal forms of multiple sclerosis. This disease also causes chronic disability and is therefore associated with high health burden in areas where HTLV-1 infection is endemic. Despite various efforts in understanding the virus and discovery of novel diagnostic markers, and cellular and viral interactions, HAM/TSP management is still unsatisfactory and mainly focused on symptomatic alleviation, and it hasn’t been explained why only a minority of the virus carriers develop HAM/TSP. This comprehensive review focuses on host and viral factors in association with immunopathology of the disease in hope of providing new insights for drug therapies or other forms of intervention.


2007 ◽  
Vol 88 (7) ◽  
pp. 2052-2063 ◽  
Author(s):  
Tamás Sperka ◽  
Gabriella Miklóssy ◽  
Yunfeng Tie ◽  
Péter Bagossi ◽  
Gábor Zahuczky ◽  
...  

Bovine leukemia virus (BLV) is a valuable model system for understanding human T-lymphotropic virus 1 (HTLV-1); the availability of an infectious BLV clone, together with animal-model systems, will help to explore anti-HTLV-1 strategies. Nevertheless, the specificity and inhibitor sensitivity of the BLV protease (PR) have not been characterized in detail. To facilitate such studies, a molecular model for the enzyme was built. The specificity of the BLV PR was studied with a set of oligopeptides representing naturally occurring cleavage sites in various retroviruses. Unlike HTLV-1 PR, but similar to the human immunodeficiency virus 1 (HIV-1) enzyme, BLV PR was able to hydrolyse the majority of the peptides, mostly at the same position as did their respective host PRs, indicating a broad specificity. When amino acid residues of the BLV PR substrate-binding sites were replaced by equivalent ones of the HIV-1 PR, many substitutions resulted in inactive protein, indicating a great sensitivity to mutations, as observed previously for the HTLV-1 PR. The specificity of the enzyme was studied further by using a series of peptides containing amino acid substitutions in a sequence representing a naturally occurring HTLV-1 PR cleavage site. Also, inhibitors of HIV-1 PR, HTLV-1 PR and other retroviral proteases were tested on the BLV PR. Interestingly, the BLV PR was more susceptible than the HTLV-1 PR to the inhibitors tested. Therefore, despite the specificity differences, in terms of mutation intolerance and inhibitor susceptibility of the PR, BLV and the corresponding animal-model systems may provide good models for testing of PR inhibitors that target HTLV-1.


Author(s):  
D.C. Hixson ◽  
J.C. Chan ◽  
J.M. Bowen ◽  
E.F. Walborg

Several years ago Karasaki (1) reported the production of type C virus particles by Novikoff ascites hepatocarcinoma cells. More recently, Weinstein (2) has reported the presence of type C virus particles in cell cultures derived from transplantable and primary hepatocellular carcinomas. To date, the biological function of these virus and their significance in chemically induced hepatocarcinogenesis are unknown. The present studies were initiated to determine a possible role for type C virus particles in chemically induced hepatocarcinogenesis. This communication describes results of studies on the biological and surface properties of type C virus associated with Novikoff hepatocarcinoma cells.Ecotropic and xenotropic murine leukemia virus (MuLV) activity in ascitic fluid of Novikoff tumor-bearing rats was assayed in murine sarcoma virus transformed S+L- mouse cells and S+L- mink cells, respectively. The presence of sarcoma virus activity was assayed in non-virus-producing normal rat kidney (NRK) cells. Ferritin conjugates of concanavalin A (Fer-Con wheat germ agglutinin (Fer-WGA), and Ricinus communis agglutinins I and II (Fer-RCAI and Fer-RCAII) were used to probe the structure and topography of saccharide determinants present on the viral envelope.


Author(s):  
L. Z. de Tkaczevski ◽  
E. de Harven ◽  
C. Friend

Despite extensive studies, the correlation between the morphology and pathogenicity of murine leukemia viruses (MLV) has not yet been clarified. The virus particles found in the plasma of leukemic mice belong to 2 distinct groups, 1 or 2% of them being enveloped A particles and the vast majority being of type C. It is generally believed that these 2 types of particles represent different phases in the development of the same virus. Particles of type A have been thought to be an earlier form of type C particles. One of the tissue culture lines established from Friend leukemia solid tumors has provided the material for the present study. The supernatant fluid of the line designated C-1A contains an almost pure population of A particles as illustrated in Figure 1. The ratio is, therefore, the reverse of what is unvariably observed in the plasma of leukemic mice where C particles predominate.


Author(s):  
U.I. Heine ◽  
G.R.F. Krueger ◽  
E. Munoz ◽  
A. Karpinski

Infection of newborn mice with Moloney leukemia virus (M-MuLV) causes a T-cell differentiation block in the thymic cortex accompanied by proliferation and accumulation of prethymic lymphoblasts in the thymus and subsequent spreading of these cells to generate systemic lymphoma. Current evidence shows that thymic reticular epithelial cells (REC) provide a microenvironment necessary for the maturation of prethymic lymphoblasts to mature T-lymphocytes by secretion of various thymic factors. A change in that environment due to infection of REC by virus could be decisive for the failure of lymphoblasts to mature and thus contribute to lymphoma development.We have studied the morphology and distribution of the major thymic cell populations at different stages of tumorigenesis in Balb/c mice infected when newborn with 0.2ml M-MuLV suspension, 6.8 log FFU/ml. Thymic tissue taken at 1-2 weekly intervals up to tumor development was processed for light and electron microscopy, using glutaraldehyde-OsO4fixation and Epon-Araldite embedding.


Author(s):  
N. Savage ◽  
A. Hackett

A cell line, UC1-B, which was derived from Balb/3T3 cells, maintains the same morphological characteristics of the non-transformed parental culture, and shows no evidence of spontaneous virus production. Survey by electron microscopy shows that the cell line consists of spindle-shaped cells with no unusual features and no endogenous virus particles.UC1-B cells respond to Moloney leukemia virus (MLV) infection by a change in morphology and growth pattern which is typical of cells transformed by sarcoma virus. Electron microscopy shows that the cells are now variable in shape (rounded, rhomboid, and spindle), and each cell type has some microvilli. Virtually all (90%) of the cells show virus particles developing at the cell surface and within the cytoplasm. Maturing viruses, typical of the oncogenic viruses, are found along with atypical tubular forms in the same cell.


Author(s):  
W. J. Hamilton

The study of RNA tumor viruses has been greatly facilitated by the use of immunochemical tagging methods. In the past these methods have been constrained to antibody conjugates with ferritin or peroxidase. In order to avoid the disadvantages of using conjugated antisera, investigators have applied the unlabeled antibody enzyme method of Sternberger to mammary tumor derived mouse cells prior to embedding for electron microscopy. The current study has successfully applied the Sternberger method to virusproducing cells and purified virus pellets after epoxy-embedding and ultrathin sectioning. The results demonstrate the distinct advantages of this “post-embedding” method for viral antigen localization.Purified Rauscher leukemia virus (RLV) and mouse mammary tumor virus (MMTV) were pelleted, fixed in buffered 2% paraformaldehyde and washed thoroughly. These were dehydrated in acetone, infiltrated and embedded in Spurr resin according to common procedures. A tumor derived cell line, Mm5mt, producing MMTV was embedded by parallel methods.


Author(s):  
W. Djaczenko ◽  
M. Müller ◽  
A. Benedetto ◽  
G. Carbone

A thickening of ER membranes in murine myeloma cells was attributed by de Harven to the assembly of intracisternal virus particles. We observed similar thickening of GER membranes in Friend leukemia cells (FLC) apparently associated with Friend leukemia virus (FLV) assembly. We reinvestigated the problem of GER involvement in FLV assembly using high pressure cryofixed FLC.FLC (745A clone growing in suspension and FF clone growing in monolayer) were immersed in Hexadecene (Fluka, Switzerland) and rapidly frozen in Balzers HPM 010 freezing machine working at 2200 bar. All cells were freeze substituted at -90°C in 2% OsO4 in absolute acetone. Serial sections cut to avoid misinterpretations due to the geometry of sections, were collected on carbon coated 100 mesh grids.


Author(s):  
Ray A. Weigand ◽  
Gregory C. Varjabedian

We previously described the intracellular localization of murine mammary tumor virus (MuMTV) p28 protein in thin sections (1). In that study, MuMTV containing cells fixed in 3% paraformaldehyde plus 0.05% glutaraldehyde were labelled after thin sectioning using ferritin-antiferritin in an unlabelled antibody technique. We now describe the labelling of murine leukemia virus (MuLV) particles using the unlabelled antibody technique coupled to ferritin-Fab antiferritin. Cultures of R-MuLV in NIH/3T3 cells were grown to 90% confluence (2), fixed with 2% paraformaldehyde plus 0.5% glutaraldehyde in 0.1 M cacodylate at pH 7.2, postfixed with buffered 17 OsO4, dehydrated with a series of etha-nols, and embedded in Epon. Thin sections were collected on nickel grids, incubated in 107 H2O2, rinsed in HEPES buffered saline, and subjected to the immunoferritin labelling procedure. The procedure included preincubation in 27 egg albumin, a four hour incubation in goat antisera against purified gp69/71 of MuLV (3) (primary antibody), incubation in F(ab’)2 fragments of rabbit antisera to goat IgG (secondary antibody), incubation in apoferritin, incubation in ferritin-Fab ferritin, and a brief fixation with 2% glutaraldehyde. The sections were stained with uranyl acetate and examined in a Siemens IA electron microscope at an accelerating voltage of 60 KV.


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