Beverly D. Roberts

Seroprevalence of HTLV-I and HTLV-II among Intravenous Drug Users and Persons in Clinics for Sexually Transmitted Diseases

Abstract Background. The human T-cell lymphotropic virus Type I (HTLV-I) is associated with adult T-cell leukemia and myelopathy, whereas HTLV-II infection has uncertain clinical consequences. We assessed the seroprevalence of these retroviruses among intravenous drug users and among patients seen at clinics for sexually transmitted diseases (STD clinics). Methods. We used serum samples that were collected in eight cities in 1988 and 1989 during surveys of human immunodeficiency virus infection among intravenous drug users entering treatment and persons seen in STD clinics. The serum samples were tested for antibodies to HTLV, and positive specimens were tested further by a synthetic peptide-based enzyme-linked immunosorbent assay to differentiate between HTLV-I and HTLV-II. Results. Among 3217 intravenous drug users in 29 drug-treatment centers, the median seroprevalence rates of HTLV varied widely according to city (range, 0.4 percent in Atlanta to 17.6 percent in Los Angeles). Seroprevalence increased ...

Cellular Compartments of Human Immunodeficiency Virus Type 1 Replication In Vivo: Determination by Presence of Virion-Associated Host Proteins and Impact of Opportunistic Infection

ABSTRACT Antigens derived from host cells are detectable in the envelope of human immunodeficiency virus type 1 (HIV-1) and result in a distinctive viral phenotype reflecting that of the host cell. An immunomagnetic capture assay targeting discriminatory host proteins was developed to differentiate between HIV-1 derived from macrophages and lymphocytes. HIV-1 propagated in macrophages or lymphocytes in vitro was selectively captured by monoclonal antibodies directed against the virally incorporated cell-type-specific host markers CD36 (macrophages) and CD26 (lymphocytes). Furthermore, by targeting these markers, virus of defined cellular origin was selectively captured from a mixed pool of in vitro-propagated viruses. This technique was further refined in order to determine the impact of opportunistic infection on HIV-1 expression from these cellular compartments in vivo. Analysis of cell-free virus purified from plasma of patients with HIV-1 infection suggested that in those with an opportunistic infection, viral replication occurred in activated lymphocytes. Interestingly, there was also significant replication in activated macrophages in those patients with untreated pulmonary tuberculosis. Thus, in addition to lymphocytes, the macrophage cellular pool may serve as an important source of cell-free HIV-1 in patients with opportunistic infections that lead to marked macrophage activation. This novel viral capture technique may allow researchers to address a wide range of important questions regarding virus-host dynamics.

Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells

OBJECTIVE To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor (TNF)-alpha, an immunoregulatory cytokine that can enhance HIV-1 replication. DESIGN Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors. METHODS TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry, and signal transduction was detected by gel shift analysis. HIV-1 activation and expression was quantitated by reverse transcriptase assay. RESULTS In the OM-10.1 promyelocytic model of chronic infection, TNF-alpha-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor (TR75) expression although 55 kD TNF receptor (TR55) levels were not dramatically altered. A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-alpha treatment. Enhanced TR75 expression on OM-10.1 cells followed the same TNF-alpha-dose dependency as that observed for HIV-1 production. An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes. Although TR55 expression was unaltered during TNF-alpha-induced HIV activation, this receptor was still involved in the viral activation process. Antibody cross-linking of TR55, in the absence of exogenous TNF-alpha, induced maximal HIV-1 expression, an up-modulation of surface TR75, and nuclear NF-kappa B activity in OM-10.1 cultures. Surprisingly, this was the case even when an antagonistic anti-TR55 antibody was used. Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-alpha-induced HIV-1 expression. CONCLUSIONS Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors, potentially influencing its own expression and altering normal immunoregulatory signal transduction.

Characterization of a B-cell immunodominant epitope of human T-lymphotropic virus type 1 (HTLV-I) envelope gp46

The immune response elicited by a synthetic peptide derived from an immunodominant external envelope region (Env-5, amino acids 242-257) of human T-lymphotropic virus type 1 (HTLV-I) was tested in a rabbit model of HTLV-I infection. The synthetic peptide elicited a strong antibody response to the HTLV-I envelope protein gp46; however, these antibodies failed to inhibit HTLV-I-mediated cell fusion. Immunized rabbits were not protected from HTLV-I infection as determined by seroconversion to viral core proteins by immunoblot, HTLV-I p24 antigen detection in lymphocyte cultures and polymerase chain reaction for the HTLV-I provirus in lymphocyte DNA. Env-5 peptide immunization failed to induce T-cell lymphocyte proliferative responses in rabbits, but induced antibody responses in T-cell deficient Balb c nu/nu mice suggesting that the antigenic determinant represented by the Env-5 peptide is primarily a B-cell epitope. These results further define an immunodominant epitope of the HTLV-I envelope protein and suggest that potential synthetic peptide vaccines against HTLV-I infection must contain multiple antigens that induce both humoral and cellular immune reactivity.

Relation between human T-lymphotropic virus type I and neurologic diseases in Panama: 1985-1990.

Human T-cell lymphotropic virus type I (HTLV-I) is endemic in the Caribbean basin and in Japan. HTLV-II, a closely related virus, is endemic in several groups of native Americans, including Panamanian Guaymi. In Panama, a nationwide HTLV-I/II seroprevalence of 1-2% has been reported. We evaluated the frequency of HTLV-I/II infection in patients with neurologic diseases admitted to state tertiary hospitals in Panama City between 1985 and 1990. Nineteen of 322 patients with eligible diagnoses had antibodies to HTLV-I/II, 17 with HTLV-I and 2 with HTLV-II. HTLV-I was associated with spastic paraparesis (13 of 23, 56.5% versus 4 of 299, 1.3%, p < 0.001) and with cerebellar syndrome (2 of 13, 15.4%) and multiple sclerosis (2 of 54, 3.7%) (p < 0.05 for both diseases compared with subject with none of these diagnoses). The two HTLV-I infected patients with cerebellar syndrome later developed spastic paraparesis. HTLV-II infection was noted in one patient with cerebellar syndrome and one with amyotrophic lateral sclerosis. All patients with other diagnoses were seronegative. Among patients with spastic paraparesis, HTLV-I-infected patients were clinically indistinguishable from seronegative subjects. There is apparently an overlapping clinical spectrum of neurologic diseases associated with HTLV-I and HTLV-II infection.