Epidermal Langerhans Cells-A Target for HTLV-III/LAV Infection

Langerhans cells (LC) are bone marrow-derived, la+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS

The leukotriene B(4) receptor functions as a novel type of coreceptor mediating entry of primary HIV-1 isolates into CD4-positive cells

The recently cloned human chemoattractant receptor-like (CMKRL)1, which is expressed in vivo in CD4-positive immune cells, has structural homology with the two chemokine receptors C-C chemokine receptor (CCR)5 and C-X-C chemokine receptor (CXCR)4, which serve as the major coreceptors necessary for fusion of the HIV-1 envelope with target cells. In view of the structural similarity, CMKRL1 was tested for its possible function as another HIV-1 coreceptor after stable expression in murine fibroblasts bearing the human CD4 receptor. The cells were infected with 10 primary clinical isolates of HIV-1, and entry was monitored by semiquantitative PCR of viral DNA. The efficiency of the entry was compared with the entry taking place in CD4-positive cells expressing either CCR5 or CXCR4. Seven of the isolates used CMKRL1 for viral entry; they were mainly of the syncytium-inducing phenotype and also used CXCR4. Entry efficiency was higher with CMKRL1 than with CXCR4 for more than half of these isolates. Three of the ten isolates did not use CMKRL1; instead, entry was mediated by both CCR5 and CXCR4. The experiments thus indicate that CMKRL1 functions as a coreceptor for the entry of HIV-1 into CD4-positive cells. In the course of this study, leukotriene B(4) was shown to be the natural ligand for this receptor (now designated BLTR), which therefore represents a novel type of HIV-1 coreceptor along with the previously identified chemokine receptors. BLTR belongs to the same general chemoattractant receptor family as the chemokine receptors but is structurally more distant from them than are any of the previously described HIV-1 coreceptors

Spectrum of Human T-Cell Lymphotropic Virus Type III Infection in Children: Recognition of Symptomatic, Asymptomatic, and Seronegative Patients

This study was done to gain insight into the clinical spectrum and immunologic disturbances resulting from infection with the human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) in children. Serum antibody to p41 antigen of HTLV-III and/or direct evidence of HTLV-III in lymphocytes was considered indicative of HTLV-III/LAV infection. In 36 children with HTLV-III/LAV infection, a wide clinical spectrum was noted, ranging from asymptomatic (seven children) to symptomatic, the latter including 14 children with the acquired immunodeficiency syndrome. Microcephaly was noted in five symptomatic infants. Immunologic dysfunction was noted in all symptomatic and in two asymptomatic children. Panhypogammaglobulinemia was noted in one child. Two asymptomatic children who were HTLV-III antibody negative had virologic evidence of HTLV-III infection. All of 20 mothers who were studied were HTLV-III antibody positive and had immunologic abnormalities but only nine were symptomatic, indicating that apparently healthy women may transmit HTLV-III/LAV infection to their offspring.(JAMA 1986;255:2299-2305