title: Attenuated and nonproductive viral transcription in the lymphatic tissue of HIV-1-infected patients receiving potent antiretroviral therapy.
abstract: Human immunodeficiency virus type 1 (HIV-1) RNA that persists in the lymphoid tissue of patients despite treatment with highly active antiretroviral therapy (HAART) may represent extracellular virions or intracellular RNAs residing within HIV-infected cells. To further characterize residual viral transcription, tonsil biopsy specimens from patients receiving long-term HAART, untreated patients, and patients undergoing 2 weeks of structured treatment interruption were analyzed by polymerase chain reaction quantification of virion-encapsidated RNA, intracellular unspliced HIV RNA (HIV UsRNA), multiply spliced HIV RNA encoding tat and rev (HIV MsRNA), and HIV DNA. Tonsil biopsy specimens from viremic patients harbored high amounts of virions, which primarily stemmed from local production, as indicated by a strong correlation of extracellular tonsillar RNA with intracellular HIV-1 nucleic acid levels but not with plasma viremia, and as shown by phylogenetic analysis of clonal env sequences from lymphoid tissue and plasma. In patients receiving HAART, intracellular HIV UsRNA persisted at significantly decreased levels, whereas HIV MsRNA and lymphoid virion levels were depleted. Thus, residual lymphoid HIV-1 RNA in patients receiving HAART indicates attenuated viral transcription in HIV-1-infected cells that lack virion production.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, Department of Medicine, University Hospital Zurich, Zurich, Switzerland. marek.fischer@.usz.ch.
authors.forename: Marek
authors.initials: M
authors.lastname: Fischer
authors.forename: Beda
authors.initials: B
authors.lastname: Joos
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Peter
authors.initials: P
authors.lastname: Ott
authors.forename: Milos
authors.initials: M
authors.lastname: Opravil
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008221:Lymphoid Tissue / Q000821:virology*; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D014158:Transcription, Genetic; D014766:Viremia / Q000821:virology
chemical_list: D012367:RNA, Viral