ABSTRACT
To date, attempts to eliminate HIV-1 infection from its latent reservoirs, a prerequisite for the development of a curative treatment strategy for HIV-1 infection, have been unsuccessful. We demonstrate that the FDA approved antifungal agent amphotericin B efficiently reactivates HIV-1 infection in THP89GFP cells, a model of HIV-1 latency in macrophages. Although amphotericin B does not directly reactivate latent HIV-1 infection in T cells (e.g., J89GFP), amphotericin-B-stimulated macrophages (THP89GFP cells or primary macrophages) when cocultured with J89GFP cells can induce HIV-1 reactivation in these cells in trans. Because of the close proximity of antigen presenting macrophages and T cells in the primary lymphoid organs, such interaction between antigen presenting macrophages and T cells are frequent, and it seems reasonable to assume that trans-reactivation strategies hold promise to also reactivate latent HIV-1 infection in vivo.
Subject(s)
Amphotericin B/pharmacology , HIV-1/drug effects , Virus Activation/drug effects , Virus Latency/drug effects , Amiloride/pharmacology , Antifungal Agents/pharmacology , Butadienes/pharmacology , Cell Line , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Gene Expression , HIV-1/physiology , Humans , Nitriles/pharmacology , Sodium-Hydrogen Exchangers/antagonists & inhibitors , Tumor Necrosis Factor-alpha/physiologyABSTRACT
Urine and peripheral blood samples from 48 human immunodeficiency virus type 1 (HIV-1) seropositive individuals (38 adults and 10 children) were evaluated for the presence of HIV-1 by cocultivation and for HIV-1 p24 antigen by ELISA. None of the urine samples contained replication-competent HIV-1; 41 (85%) of 48 simultaneously obtained peripheral blood mononuclear cell samples contained replication-competent HIV-1. None of 26 urine samples available for analysis contained HIV-1 p24 antigen as determined by ELISA; 12 (34%) of 35 simultaneously obtained peripheral blood samples had detectable serum HIV-1 p24 antigen. Two of the individuals studied had HIV nephropathy, three had pyuria, and five had microscopic hematuria. Culture sensitivity was maximal when mycostatin (and not amphotericin B) was used as an antifungal agent. Our findings indicate that urine from HIV-1-seropositive individuals is unlikely to contain infectious HIV-1. This would imply that the risk of transmission of HIV-1 by urine is low to nonexistent.
Subject(s)
Gene Products, gag/urine , HIV Seropositivity/urine , HIV-1/isolation & purification , Viral Core Proteins/urine , Adult , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Gene Products, gag/blood , HIV Core Protein p24 , HIV Seropositivity/blood , HIV Seropositivity/microbiology , HIV-1/immunology , Humans , Infant , Middle Aged , Urine/microbiology , Viral Core Proteins/blood , Viremia/blood , Viremia/microbiology , Viremia/urine , Virus ReplicationABSTRACT
We examined retinal tissue from eight human immunodeficiency virus type 1 (HIV-1) seropositive patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex for evidence of dual infection with HIV-1 and cytomegalovirus. Culture demonstrated simultaneous infection with HIV-1 and cytomegalovirus in two of 13 retinal specimens. This was confirmed by both immunofluorescence and immunohistochemical staining. Moreover, coinfection of individual cells with cytomegalovirus and HIV-1 was observed by immunohistochemical staining. Infection of retina with cytomegalovirus or HIV-1 alone occurred in one and six of the 13 retinal specimens, respectively. HIV-1 antigens were present on scattered cells in all layers of the retina and on retinal vascular endothelium. HIV-1 was isolated from retinal tissue derived from eyes both with and without gross ocular lesions. Cytomegalovirus antigens were found in all layers of the retina, but not on vascular endothelial cells. The atypically rapid clinical progression of retinitis in one of the patients with dual HIV-1 and cytomegalovirus infection suggests the possibility that interactions between these two viruses may influence retinal disease in patients with AIDS.
Subject(s)
Acquired Immunodeficiency Syndrome/microbiology , Cytomegalovirus/isolation & purification , HIV-1/isolation & purification , Retina/microbiology , AIDS-Related Complex/microbiology , Acquired Immunodeficiency Syndrome/complications , Adult , Cytomegalovirus Infections/complications , Female , Fluorescent Antibody Technique , HIV Seropositivity/microbiology , Humans , Immunohistochemistry , Male , Retinitis/complicationsSubject(s)
Cytomegalovirus Infections , Retinitis/etiology , Thymidine/analogs & derivatives , Acquired Immunodeficiency Syndrome/complications , Adult , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Fundus Oculi , Humans , Male , Retinitis/pathology , Thymidine/therapeutic use , ZidovudineABSTRACT
Interactions between human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS, and human cytomegalovirus (CMV), a frequent opportunistic agent in AIDS, were studied in vitro. Coinfection of H9 cells with HIV-1 enhances productive CMV infection, as measured by immunofluorescence using monoclonal antibodies to late CMV proteins, slot-blot hybridization for CMV DNA, and cytopathic effects of CMV on human embryonic lung cells. Experiments using vaccinia virus recombinants and Jurkat cells transfected with the transactivating (tat) gene of HIV-1 suggest that this enhancement is not mediated primarily by the tat protein. In addition, coinfection of H9 cells or a monocyte cell line with CMV and HIV-1 results in enhanced HIV-1 replication, as measured in a virus-yield assay or by radioimmunoassay for the p24 antigen of HIV-1. The interactions between HIV-1 and CMV are thus bidirectional.