Limited evolution of human immunodeficiency virus type 1 in the thymus of a perinatally infected child.

Abstract

Involvement of the thymus during human immunodeficiency virus (HIV) infection may impair production of naive lymphocytes leading to more rapid depletion, but the characteristics of primary strains in the thymus are not well studied because of the unavailability of tissue in living individuals. We studied the characteristics of HIV type 1 (HIV-1) in a 5-year old perinatally infected child with thymitis and compared the genomic sequences of the HIV-1 C2-V5 region of the env gene in the thymic tissue and peripheral blood. The thymus harbored predominantly viral sequences close to the founder HIV-1 variant that circulated in the blood at 2 and 3 months of age, whereas the peripheral blood virus at 5 years of age had evolved extensively. Viral sequences from circulating CD8(+) T cells at 5 years of age phylogenetically clustered with those from the thymic tissue. These results indicate the existence of a distinct thymic viral reservoir and suggest that circulating CD8(+) T cells were infected in the thymus, presumably at the CD4(+)CD8(+) thymocyte stage. They also demonstrate that not all thymic HIV infections will necessarily lead to severe thymic dysfunction. The characteristics of the virus strain seeding the thymus may dictate the rate of disease progression.