Frequent Identification of HIV-1 DNA in Bronchoalveolar Lavage Cells Obtained from Individuals with the Acquired Immunodeficiency Syndrome

Abstract

Tissue macrophages are recognized as a cellular target for infection with the human immunodeficiency virus type 1 (HIV-1). To characterize the nature of this cell-retrovirus interaction within the lower respiratory tract we analyzed fluid and cells obtained by bronchoalveolar lavage (BAL) of eight individuals with acquired immunodeficiency syndrome (AIDS) who were undergoing diagnostic fiberoptic bronchoscopy. Of these eight individuals, seven had active infection with Pneumocystis carinii; one had suspected cytomegalovirus pneumonitis. At the time of study two were receiving the antiretroviral drug zidovudine (azidothymidine [AZT]). HIV-1 could not be isolated from any of the eight samples of BAL fluid concentrated by ultracentrifugation through 20% sucrose. HIV-1 antigen (p24) was detected in one of eight samples of concentrated BAL fluid but could not be found in eight samples of media conditioned by overnight incubation with adherent BAL cells. Despite the infrequent detection of HIV-1 antigen it was possible to identify HIV-1 genomic sequences by the use of a DNA amplification technique, the polymerase chain reaction, in all eight BAL cell preparations. In BAL cells adherent for up to 5 days in culture this method detected retroviral DNA that hybridized to a complementary pair of primers located in the env and gag gene regions of HIV-1. These studies demonstrate the uniform presence of HIV-1 harboring cells within the airways of the lung in individuals with AIDS and active respiratory infection and may have implications for local organ defense.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinoid-Dependent Restriction of Human Immunodeficiency Virus Type 1 Replication in Monocytes/Macrophages

“…It is conceivable that latently infected monocytes and tissue macrophages, such as alveolar macrophages (40,50), contribute to the rapid emergence of plasma viremia seen with the cessation of HAART. Perhaps potent myeloid-selective activators of HIV-1, such as retinoid antagonists, will be useful in specifically reactivating virus expression in latently infected macrophages, contributing to a decrease in the size of this important viral reservoir.…”

HIV-1 proviral DNA copy number in peripheral blood leucocytes and bronchoalveolar lavage cells of AIDS patients

“…by PCR in the BAL cells of 100% (8/8) of HIV+ individuals, but the virus could not be recovered from any of these lung cells by co-cultivation [13].…”

“…The most sensitive technique for the detection of HIV infection is the polymerase chain reaction (PCR) [10][11][12][13]. HIV proviral DNA has been detected by PCR in the BAL cells obtained from 47% (21/44) [11] to 65% (41/63) [12] of AIDS patients.…”

Activation-Inactivation of HIV-1 in the Lung

“…In HIV-1-infected individuals, HIV-1 is detectable in total (unseparated) bronchoalveolar cells [15,16,20,44,77], in purified alveolar macrophages [6,15,40,44,47,62,69,70,77], and in alveolar lymphocytes [75]. For bronchoalveolar cells, viral cocultures, which determine capacity for transmission of HIV-1 in vitro, are positive in 9-59% of HIV-1-infected persons [15,20,77].…”

“…For bronchoalveolar cells, viral cocultures, which determine capacity for transmission of HIV-1 in vitro, are positive in 9-59% of HIV-1-infected persons [15,20,77]. By DNA PCR, which detects latent virus, 50-86% of HIV-1-infected individuals harbor HIV-1 in bronchoalveolar cells [16,44,69,77]. These findings suggest that HIV-1 exists predominantly in a latent state in bronchoalveolar cells at least when individuals are not concurrently infected with opportunistic infections.…”