Formation of IgE-binding factors by T cells of patients infected with human immunodeficiency virus type 1.

Peripheral blood mononuclear cells of 10 out of 26 patients with human immunodeficiency virus type 1 (HIV-1) released IgE-binding factors, as determined by two independent assays. The formation of the factors by the mononuclear cells was enhanced by incubation of the cells with homologous IgE. In the presence of IgE, peripheral blood mononuclear cells from 15 of the 26 patients formed a detectable amount of IgE-binding factors, whereas those of normal individuals of allergic rhinitis patients failed to do so. The major source of IgE-binding factors was the T cells of the HIV-1-infected patients. The CD8+ T cells from a HIV-1-infected patient formed IgE-binding factors upon incubation with IgE, and type II receptors for Fc epsilon were detected on both CD4+ T cells and CD8+ T cells in one of five patients studied. It was also found that culture supernatants of mononuclear cells from HIV-1-infected patients released soluble factors that induce normal human T cells to form IgE-binding factors. The results suggest that lymphocytes of some HIV-1-infected patients are activated to produce lymphokines regulating formation of IgE-binding factors.     

Lysis of human immunodeficiency virus infected cells by TPA-type and non-TPA type tumor promoters

We reported previously that TPA facilitates the replication of human immunodeficiency virus (HIV) and has a selective lethal effect on HIV-infected cells by a cytopathic effect induced by HIV. We have now studied the cytopathic effects of TPA-type tumor promoters (teleocidin, aplysiatoxin, and TPA) and the non-TPA type tumor promoters (palytoxin and thapsigargin) on MOLT-4/HIVHTLV-IIIB cells. All TPA-type and non-TPA type tumor promoters tested except palytoxin stimulated in HIV production three- to sevenfold, and caused more lysis of MOLT-4/HIVHTLV-IIIB cells than of the parental MOLT-4 cells. Fifty percent of the MOLT-4/HIVHTLV-IIIB cells were killed by teleocidin, aplysiatoxin, TPA and thapsigargin at concentrations of 2.0, 2.0, 1.0 and 10 ng/ml respectively, and by palytoxin at the very low concentration of 2.0 pg/ml. Moreover, combinations of one TPA-type tumor promoter and one non-TPA type tumor promoter--but not the combination of two TPA-type tumor promoters--had additive lethal effects, supporting the idea that TPA-type and non-TPA type tumor promoters exert their cytolytic effects by different mechanisms. These latter effects may be due to production of prostaglandin E2, which is commonly induced by both types of tumor promoters.     

Cytokine production by endothelial cells infected with human T cell lymphotropic virus type I.

OBJECTIVE: To investigate the ability of human T cell lymphotropic virus type I (HTLV-I) to infect endothelial cells and induce cytokine production by these cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were cocultured with HTLV-I infected T cell line (MT-2 cells) or uninfected T cell line (CEM cells). RESULTS: Following coculture with MT-2 cells, endothelial cells expressed HTLV-I specific core antigens. Endothelial cells cocultured with MT-2 cells produced significant amounts of several cytokines, including interleukin (IL)-1 alpha, IL-6, granulocyte colony stimulating factor (G-CSF), and granulocyte/macrophage colony stimulating factor (GM-CSF), compared with endothelial cells cocultured with CEM cells. Coculturing of endothelial cells with MT-2 and CEM cells failed to produce detectable amounts of IL-1 beta and tumour necrosis factor alpha (TNF-alpha). The production of cytokines by endothelial cells cocultured with MT-2 cells was more persistent than that by endothelial cells cocultured with CEM cells after several passages. Furthermore, the production was blocked by cocultivation of endothelial cells and MT-2 cells using the Millicell system. Finally, after cocultivation of endothelial cells and MT-2 cells, endothelial cells positive for HTLV-I antigen were stained by anti-GM-CSF antibody. CONCLUSIONS: HTLV-I can infect endothelial cells, resulting in their active production of several cytokines, such as IL-1 alpha, IL-6, G-CSF, and GM-CSF. These findings strongly suggest that the excess production of these cytokines by HTLV-I infected endothelial cells may be involved in the pathogenesis of HTLV-I associated inflammatory diseases.     

Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1

HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.     

Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus

Human immunodeficiency virus (HIV) elicits the production of virus-specific antibodies in infected individuals. We investigated the ability of serum from HIV-infected individuals to mediate antibody-dependent cellular cytotoxicity in an in vitro 51Cr release assay system. Fresh peripheral blood mononuclear cells from healthy donors seronegative for HIV were used as cellular effectors against HIV-infected and uninfected H9 target cells in the presence of serum from HIV-infected or uninfected donors. Serum from HIV-infected, but not uninfected, donors significantly augmented cytolysis of virus-infected targets (P less than .005). There was no augmented killing of uninfected H9 cells with sera from either group. Studies using serum from mice that had been immunized with synthetic peptides from the HIV envelope region suggested that this response is directed, at least in part, at several determinants of the transmembrane portion of the HIV envelope glycoprotein.     

Selenium and interleukins in persons infected with human immunodeficiency virus type 1

An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.     

Risk factors for community-acquired pneumonia among persons infected with human immunodeficiency virus

Two hundred eleven adults with human immunodeficiency virus (HIV) infection hospitalized for community-acquired pneumonia, including Pneumocystis carinii pneumonia (PCP; patients), and 192 matched HIV-infected hospitalized patients without pneumonia (controls) were interviewed to determine risk factors for pneumonia. Multivariate logistic regression showed that patients were less likely than controls to have used trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.12-0.41) and more likely to have been hospitalized previously with pneumonia (OR, 6.25; CI, 3.40-11.5). Patients were also more likely than controls to have gardened (OR, 2.24; CI, 1.00-5.02) and to have camped or hiked (OR, 4.95; CI, 1.31-18.7), but stratified analysis by etiologic agent showed this association only for PCP. These findings reconfirm the efficacy of TMP-SMZ in preventing community-acquired pneumonia. In addition, hospitalization for pneumonia might represent a missed opportunity to encourage HIV-infected patients to enter into regular medical care and to adhere to prescribed antiretroviral and prophylaxis medications.     

Cervical and prostate primary epithelial cells are not productively infected but sequester human immunodeficiency virus type 1

Primary prostate and cervical epithelial cells and epithelial cell lines were examined for human immunodeficiency virus type 1 (HIV-1) infection or transmission to peripheral blood mononuclear cells (PBMC). Neither cell-free nor cell-associated HIV-1 infected primary epithelial cells or cell lines. Pretreatment of HIV-1 to enhance CD4-independent entry did not augment infection. Cell surface expression was detected for galactosyl ceramide but not for CC-chemokine receptor 5, CXC-chemokine receptor 4, or CD4. The ability to transfer HIV-1 to resting or activated PBMC was tested by culturing with rinsed or trypsinized and replated HIV-1-exposed epithelial cells. Virus was not recovered from the rinsed or replated cocultures with resting PBMC; however, activated PBMC recovered HIV-1 from rinsed epithelial cells and rarely from replated epithelial cells. Although urogenital epithelial cells are not infected, these data suggest that they can transfer virus to activated immune cells and have implications for sexual transmission of HIV-1.     

Simultaneous infections with human T cell leukemia virus type I and the human immunodeficiency virus

Four adults form four separate households were found to have simultaneous retroviral infections with human T cell leukemia virus type I (HTLV-I) and human immunodeficiency virus (HIV). These individuals were seropositive for the HTLV-I env transmembrane protein p21E, and all had antibodies to the HTLV-I core polypeptide p24. All four patients also had antibodies to the HIV env transmembrane polypeptide p41E and to the HIV core polypeptide p24. HTLV-I was isolated from peripheral blood lymphocytes of all four individuals, and both viruses were isolated from two of them. Evidence of HIV transmission was noted in the family contacts. Eight of 10 children of these four adults were seropositive for HIV, presumably because of perinatal transmission from infected mothers. Two of five spouses of these adults were examined; these spouses had antibodies to HIV and were positive for virus. No evidence of HTLV-I transmission was noted in these families.     

Virus levels in untreated African infants infected with human immunodeficiency virus type 1

In developed areas, human immunodeficiency virus (HIV)-infected infants have high virus levels and rapidly progress to death. HIV levels were assessed in 1994-1997 in untreated infants in Malawi by analysis of dried blood spots tested by nucleic acid silica-bound amplification. Of 24 umbilical cord blood (CB)-positive samples, 83% had >10,000 copies/mL. The median virus level was 78,000 copies/mL. First positive sample median levels were 355,000 copies/mL among 52 perinatally infected infants and 130,000 copies/mL among 43 infants infected by breast-feeding. Virus levels were stable, and initial levels predicted levels 1 year after infection (P=.005), at which time levels did not significantly differ among in utero, perinatally, or postnatally infected infants. Thus, neither age at infection nor route of infection significantly influenced HIV levels measured 1 year after infection. Most (87%) CB-positive infants were infected before labor onset, since virus levels greatly exceeded those expected in their mothers.     

Haemophilus influenzae type b immunization in adults infected with the human immunodeficiency virus

The purpose of this study was to assess the influence of Haemophilus influenzae type b conjugate vaccine on HIV-1 RNA level, CD4 count, and anti-Hib polysaccharide (PRP) antibody concentration. Eighty HIV-infected adults were randomized to receive Hib conjugate vaccine or not. Twenty HIV-seronegative controls were also vaccinated. Blood samples were taken before and after vaccination, with a follow-up period of 6 months. HIV infection markers and anti-PRP antibodies were monitored. There was no change in either HIV-1 viremia or CD4 count after vaccination. Immunization immunogenicity was superior in HIV-uninfected than in HIV-infected individuals (p < 0.01). Hib vaccination was safe but induced suboptimal antibody response in HIV-infected adults.     

Internalization of human immunodeficiency virus type I and other retroviruses by megakaryocytes and platelets

Direct infection of megakaryocytes and platelets by human immunodeficiency virus type I (HIV-I) or other retroviruses has not been demonstrated. To determine whether this could occur, murine bone marrow was co-cultivated with the amphotropic retrovirus-producing cell line PA317-N2, and freshly isolated normal human bone marrow and platelets were co-cultivated with HIV-infected H9 cells. In each case, ultrastructural analyses showed viruses within megakaryocytes and platelets. In murine specimens, the uptake of retrovirus was avid at all stages of differentiation. In human specimens, viral uptake was less frequent. These results suggest that direct infection of megakaryocytes could play a role in the pathophysiology of HIV-associated disease. In addition, these observations suggest that cells of the megakaryocyte lineage could serve as target cells in gene transfer experiments using retroviral-based vectors.     

Biphasic decay of latently infected CD4+ T cells in acute human immunodeficiency virus type 1 infection

Latent infection of resting CD4(+) T cells represents a major barrier to eradication of human immunodeficiency virus type 1 (HIV-1). The establishment and rate of decay of latent HIV-1 in resting CD(+) T cells from 9 acute seroconverters, 7 of whom began to receive highly active antiretroviral therapy (HAART) shortly after presentation, were studied. Before the initiation of therapy, these patients had very high frequencies of latently infected CD4(+) T cells, with a median frequency of 205 infectious units per million resting CD4(+) T cells. These values are > or =1 log higher than those seen in chronically infected patients who are not undergoing HAART. The number of latently infected cells declined dramatically after initiation of HAART but then tended to level off at a low but stable level. The biphasic decay of latent HIV in resting CD4(+) T cells in acute seroconverters supports current models of pre- and postintegration latency.     

Macrophage-active colony-stimulating factors enhance human immunodeficiency virus type 1 infection in bone marrow stem cells.

To define the relationship between human immunodeficiency virus type 1 (HIV-1) infection in hematopoietic stem cells and virus production by their progeny, we performed kinetic studies infecting bone marrow (BM) stem cells and culturing them in the presence of hematopoietic growth factors. CD34-positive (CD34+), CD4-negative (CD4-) BM cells were isolated and infected in vitro with the monocytotropic HIV-1JR-FL strain or the laboratory-maintained HTLV-IIIB strain at a high multiplicity of infection. The cells were susceptible to productive infection only with HIV-1JR-FL, and virus production as measured by p24 protein release was markedly increased (more than fivefold) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). Macrophage CSF (M-CSF) was less stimulatory and granulocyte CSF (G-CSF) had no effect on virus production. Virus production coincided with proliferation of mononuclear phagocytes but was not related to granulocytic proliferation in G-CSF-treated BM cultures. Although peak virus production from GM-CSF-treated macrophages occurred 2 to 3 weeks after infection, peak virus production in infected stem cells was observed 5 to 6 weeks after. Enhancement in virus production had a more rapid onset when CD34+/CD4- cells were cultured in the presence of both GM-CSF and IL-3 for 7 or 14 days. Under these conditions there was a 10-fold enhancement in virus production after 7 days of preincubation and a 50-fold enhancement after 14 days. These data indicate that while the stem cell compartment may be susceptible to infection with a monocytotropic HIV-1 strain, productive and sustained infection is realized only after macrophage differentiation. The lack of effect of G-CSF on virus production is likely because of the limited effect of this hematopoietin on mononuclear phagocyte generation and function.