Università della Svizzera italiana

Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice

Hauber, Ilona ; Hofmann-Sieber, Helga ; Chemnitz, Jan ; Dubrau, Danilo ; Chusainow, Janet ; Stucka, Rolf ; Hartjen, Philip ; Schambach, Axel ; Ziegler, Patrick ; Hackmann, Karl ; Schröck, Evelin ; Schumacher, Udo ; Lindner, Christoph ; Grundhoff, Adam ; Baum, Christopher ; Manz, Markus G. ; Buchholz, Frank ; Hauber, Joachim

In: Plos pathogens, 2013, vol. 9, no. 9, p. e1003587

Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro,...

Università della Svizzera italiana

HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- gamma c-/- Mice

Villaudy, Julien ; Wencker, Mélanie ; Gadot, Nicolas ; Gillet, Nicolas A. ; Scoazec, Jean-Yves ; Gazzolo, Louis ; Manz, Markus G. ; Bangham, Charles R. M. ; Duc Dodon, Madeleine

In: Plos pathogens, 2011, vol. 7, no. 9, p. e1002231

Alteration of early haematopoietic development is thought to be responsible for the onset of immature leukemias and lymphomas. We have previously demonstrated that TaxHTLV-1 interferes with ß- selection, an important checkpoint of early thymopoiesis, indicating that human T-cell leukemia virus type 1 (HTLV-1) infection has the potential to perturb thymic human αβ T-cell development. To...

Università della Svizzera italiana

Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc −/− mice improves engraftment of human hematopoietic cells in humanized mice

Strowig, Till ; Rongvaux, Anthony ; Rathinam, Chozhavendan ; Takizawa, Hitoshi ; Borsotti, Chiara ; Philbrick, William ; Eynon, Elizabeth E. ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 32, p. 13218-13223

Transplantation of human hematopoietic stem cells into severely immunocompromised newborn mice allows the development of a human hematopoietic and immune system in vivo. NOD/scid/γc−/− (NSG) and BALB/c Rag2−/ −γc−/− mice are the most commonly used mouse strains for this purpose and a number of studies have demonstrated the high value of these model systems in areas spanning from...

Università della Svizzera italiana

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Willinger, Tim ; Rongvaux, Anthony ; Takizawa, Hitoshi ; Yancopoulos, George D. ; Valenzuela, David M. ; Murphy, Andrew J. ; Auerbach, Wojtek ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2390-2395

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and...

Università della Svizzera italiana

Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

Rongvaux, Anthony ; Willinger, Tim ; Takizawa, Hitoshi ; Rathinam, Chozhavendan ; Auerbach, Wojtek ; Murphy, Andrew J. ; Valenzuela, David M. ; Yancopoulos, George D. ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2378-2383

Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial...

Università della Svizzera italiana

Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation

Takizawa, Hitoshi ; Regoes, Roland R. ; Boddupalli, Chandra S. ; Bonhoeffer, Sebastian ; Manz, Markus G.

In: Journal of experimental medicine, 2011, vol. 208, no. 2, p. 273-284

Hematopoietic stem cells (HSCs) maintain blood production. How often mouse HSCs divide and whether each HSC contributes simultaneously, sequentially, or repetitively to hematopoiesis remains to be determined. We track division of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)–labeled HSC in vivo. We found that, in steady-state mice, bone marrow cells capable of...