HIV-1 transgenic expression in mice induces selective atrophy of fast-glycolytic skeletal muscle fibers.
Human immunodeficiency virus (HIV)-induced wasting syndrome, characterized by weakness and severe loss of muscle mass, is a common condition of patients with advanced acquired immunodeficiency syndrome (AIDS). The homozygous HIV-1 transgenic mouse line Tg26 reproduces the wasting syndrome of AIDS patients, thus constituting a valid animal model to characterize the muscle phenotype induced by HIV infection. In this study, we identified a selective atrophy of fast-glycolytic myofibers in skeletal muscles of homozygous HIV-1 transgenic mice, whereas the more oxidative fiber types are spared. In agreement with this, muscles enriched in fast-glycolytic myofibers such as the extensor digitorum longus and gastrocnemius, but not those rich in oxidative fibers such as the soleus, exhibited a reduced muscle size in homozygous HIV-1 transgenic mice compared to their littermate control counterparts. Additionally, muscles of heterozygous HIV-1 transgenic mice displayed increased inflammation and blunted myofiber growth in an injury-induced muscle regeneration process. Since no myogenic intrinsic defect was observed in satellite cells from the transgenic mice, these results support the notion of an inflammation-mediated, fiber-type-specific inhibition of muscle growth in the presence of the HIV-1 transgene.
Serrano
Antonio L
AL
Program on Differentiation and Cancer, Centre for Genomic Regulation, UPF/PRBB, Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas, 08003 Barcelona, Spain. antonio.serrano@crg.es
Jardi
Merce
M
Suelves
Monica
M
Klotman
Paul E
PE
Munoz-Canoves
Pura
P
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000818:Animals; D049109:Cell Proliferation; D015870:Gene Expression; D015497:HIV-1 / Q000235:genetics*; D006579:Heterozygote; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D019076:Transgenes