HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy

Abstract

In situ hybridization with a 35S-labeled probe of cryosections from 14 lymph nodes of HTLV-III/LAV-seropositive individuals with lymphadenopathy showed the presence of rare cells containing HTLV-III RNA at levels consistent with virus replication. Positive cells were observed at a frequency of only 1-10 per section. In all lymph nodes studied, including those showing follicular hyperplasia or involution, most of the cells expressing viral RNA were present in the follicular areas. Only a minority of such cells were found outside the follicles. The nature of the follicular, virus-replicating cells was not evident from the processed cryosections. After prolonged autoradiography, another pattern of hybridization was observed, suggesting low levels of viral RNA diffusely distributed throughout most, but not all, follicles. This may represent extracellular virus and/or virus-antibody complexes, but was not consistent with intracellular viral RNA or phagocytosed virus particles. Comparison of hybridization levels in relation to histology suggested a decrease in both the number of HTLV-III replicating cells as well as in the diffusely distributed viral RNA with progression of follicular involution. Our observations indicate that in HTLV-III-infected subjects, lymph node follicles are an important site of virus replication and trapping, suggesting a decisive role of the virus in the characteristic reactive and cytopathogenic changes of HTLV-III-associated lymphadenopathy.