Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic virus type 1

We and others have recently uncovered the existence of human T-cell lymphotropic virus type 3 (HTLV-3), the third member of the HTLV family. We have now sequenced the full-length HTLV-3 Pyl43 provirus. As expected, HTLV-3 Pyl43 contains open reading frames corresponding to the gag, pol, env, tax, and rex genes. Interestingly, its long terminal repeat (LTR) includes only two Tax-responsive elements, as is the case for type 3 simian T-cell lymphotropic viruses (STLV-3). Phylogenetic analyses reveal that HTLV-3 Pyl43 is closely related to central African STLV-3. Unexpectedly, the proximal pX region of HTLV-3 Pyl43 lacks 366 bp compared to its STLV-3 counterpart. Because of this deletion, the previously described RorfII sequence is lacking. At the amino acid level, Tax3

Section: Discussionmentioning

confidence: 99%

Human T-Cell Lymphotropic Virus Type 3: Complete Nucleotide Sequence and Characterization of the Human Tax3 Protein

Calattini

Chevalier

Duprez

et al. 2006

“…Rabbits proved to be an effective model for HTLV-1 infection (1,65). In addition, monkeys and rats have been used to analyze the in vivo proliferation of HTLV-1-infected cells (7,55). Furthermore, immunodeficient mouse strains were also able to engraft some HTLV-1-immortalized cell lines (13,24).…”

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confidence: 99%

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

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.

“…However, the life expectancy of a lymphocyte is not an intrinsic property of the cell but is determined by factors such as the environment, viral infections, and the presence or absence of another, competing, cell population. We previously studied lymphocyte homeostasis, more particularly, lymphocyte proliferation and death, in different animal models of chronic leukemia, including sheep infected by the bovine leukemia virus (BLV) (7)(8)(9). In this model, proliferation was estimated by intravenous injection of bromodeoxyuridine (BrdU), a thymidine analog which is incorporated into the newly synthesized DNA via the pyrimidine salvage pathway.…”

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confidence: 99%

Peripheral Blood B-Cell Death Compensates for Excessive Proliferation in Lymphoid Tissues and Maintains Homeostasis in Bovine Leukemia Virus-InfectedSheep

Debacq

Gillet

Asquith

et al. 2006

Self Cite

The size of a lymphocyte population is primarily determined by a dynamic equilibrium between cell proliferation and death. Hence, lymphocyte recirculation between the peripheral blood and lymphoid tissues is a key determinant in the maintenance of cell homeostasis. Insights into these mechanisms can be gathered from large-animal models, where lymphatic cannulation from individual lymph nodes is possible. In this study, we assessed in vivo lymphocyte trafficking in bovine leukemia virus (BLV)-infected sheep. With a carboxyfluorescein diacetate succinimidyl ester labeling technique, we demonstrate that the dynamics of lymphocyte recirculation is unaltered but that accelerated proliferation in the lymphoid tissues is compensated for by increased death in the peripheral blood cell population. Lymphocyte homeostasis is thus maintained by biphasic kinetics in two distinct tissues, emphasizing a very dynamic process during BLV infection.In vertebrates, continuous recirculation of lymphocytes from blood through tissues and lymph nodes is critical for protection of the host during pathological inflammatory processes, as well as physiological emigration of lymphocytes that participate in immune surveillance (1,4,6,11,16,33). The network of exchange between blood and lymph through the lymph node is absolutely required to maintain normal cell homeostasis. The presence of homeostatic control of lymphocyte numbers ensures an equilibrium where cell production equals cell loss. In an immune system where lymphocyte production is continuous and the total number of cells is constant, each newly produced lymphocyte can only survive if another one dies; i.e., the rate of peripheral cell renewal depends on the life span of peripheral cells. However, the life expectancy of a lymphocyte is not an intrinsic property of the cell but is determined by factors such as the environment, viral infections, and the presence or absence of another, competing, cell population. We previously studied lymphocyte homeostasis, more particularly, lymphocyte proliferation and death, in different animal models of chronic leukemia, including sheep infected by the bovine leukemia virus (BLV) (7-9). In this model, proliferation was estimated by intravenous injection of bromodeoxyuridine (BrdU), a thymidine analog which is incorporated into the newly synthesized DNA via the pyrimidine salvage pathway. Although BrdU uptake by cells might occur in blood, its incorporation is thought to occur mainly, if not exclusively, in lymphoid tissues such as the lymph nodes, the spleen, or the bone marrow (7). By this approach, the estimated B-cell proliferation rates in infected and control sheep were 0.020 day Ϫ1 and 0.011 day Ϫ1 , respectively, meaning that 2.0 and 1.1% of the cells were produced by proliferation in 1 day. In contrast, the death rates of BrdU-labeled cells were not significantly different between the two categories of animals (average death rate, 0.089 day Ϫ1 versus 0.094 day Ϫ1 , respectively). The imbalance created by the net increase in proliferation ...