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.