Transgenic Mice Expressing Human Immunodeficiency Virus Type 1 in Immune Cells Develop a Severe AIDS-Like Disease

Abstract

We have constructed transgenic (Tg) mice expressing the entire human immunodeficiency virus type 1 (HIV-1) coding sequences in cells targeted by HIV-1 infection in humans. These Tg mice developed a severe AIDS-like disease leading to early death (<1 month). They developed muscle wasting, severe atrophy and fibrosis of lymphoid organs, tubulointerstitial nephritis, and lymphoid interstitial pneumonitis. In addition the expression of RANTES was increased in various tissues of these Tg mice relative to that in the normal controls. Disease appearance was correlated with the levels of transgene expression. The numerous pathologies observed in these mice are remarkably similar to those observed in human AIDS and, more specifically, in pediatric AIDS.

HIV-1 Nef Is Associated with Complex Pulmonary Vascular Lesions in SHIV-nef–infected Macaques

“…Although these mice develop right ventricular hypertrophy and show an increase in the percentage of muscularized pulmonary arteries with increased perivascular collagen deposition, they are remarkable for not developing plexiform lesions or intimal fibrosis of the pulmonary arteries (32). Transgenic mice expressing the entire HIV-1-coding sequence under the control of the CD4 promoter develop a severe AIDS-like disease and a lymphoid interstitial pneumonitis as well (33). These studies highlight the relevance of our identification of HIV-1 Nef as a potential contributor to advanced pulmonary vascular remodeling and plexiform lesions in HIV-associated pulmonary hypertension.…”

Co-infection withMycobacterium tuberculosisand human immunodeficiency virus: an overview and motivation for systems approaches

“…While CD4 depletion is clearly important in HIV-1 pathogenesis, HIV-1 has additional effects on the immune system that are not captured in this model (apoptosis, disruption of lymph node architecture, depletion of M. tuberculosis-specific T cells and effects on macrophage function). Therefore, more realistic models have been developed, including Nef transgenic mice (Hanna et al, 1998a(Hanna et al, , b, 2009) and humanised bone marrowliver-thymus (BLT) mice (Sun et al, 2007;Denton et al, 2008Denton et al, , 2010) that support the entire life cycle of HIV-1 and thus may become valuable tools in understanding aspects of tuberculosis and HIV-1 co-infection.…”

Viruses evolution – an attempt of non-linear prognosis

“…7. Трансгенная при помощи кДНК ВИЧ мышь с внешне регистрируемыми проявлениями болезни в возрасте 20 дней (справа) и такая же нетрансгенная (слева) [80] инфекции среди госпитализированных в отделени ях интенсивной терапии и т. д. [73 ].…”

“…И поя вились мыши, болеющие, ну не СПИДом в чистом виде, но весьма тяжело, с экспрессией генома ВИЧ (рис. 7) и передачей такового в поколениях [79,80 ]. Мыши (конечно, не лабораторные), несущие в своем геноме информацию на продукцию вирусов для человека и продуцирующие такие вирусы, выглядят весьма впечатляюще.…”