Desmond J. Martin

Reduced Expression of Interleukin-8 Receptors A and B on Polymorphonuclear Neutrophils from Persons with Human Immunodeficiency Virus Type 1 Disease and Pulmonary Tuberculosis

The expression of the two human interleukin (IL)-8 receptors, designated IL-8RA (CXCR-1) and IL-8RB (CXCR-2), on the surface of whole blood polymorphonuclear leukocytes (PMNL) was determined by use of receptor-specific monoclonal antibodies and flow cytometry. Sixteen subjects each were included in 4 study groups: healthy blood donors (ND), patients with pulmonary tuberculosis (TB), human immunodeficiency virus type 1-seropositive patients (HIV), and HIV-1-seropositive subjects with pulmonary tuberculosis (HIV/TB). A significant reduction in the percentage of PMNL expressing IL-8RA and IL-8RB and in their respective fluorescence intensities was found in TB, HIV, and HIV/TB groups compared with that obtained for the ND group. The greatest down-regulation of both receptors occurred in the HIV/TB group. Furthermore, associated with this reduced expression of IL-8 receptors was impairment of both intracellular calcium flux and migration of PMNL in response to IL-8 in a group of HIV/TB patients compared with that in healthy persons.

High Human Immunodeficiency Virus Type 1 RNA Load in the Cerebrospinal Fluid from Patients with Lymphocytic Meningitis

Thirty-seven matched cerebrospinal fluid (CSF) and plasma samples from 34 human immunodeficiency virus type 1 (HIV-1)-infected patients with suspected meningitis were analyzed for levels of HIV-1 RNA and markers of inflammation. Patients with tuberculous (n = 9) or cryptococcal (n = 6) meningitis had the highest CSF virus loads, which in many cases exceeded the levels in plasma, compared with patients with meningococcal meningitis (n = 3), aseptic meningitis (n = 8), tuberculoma (n = 2), or AIDS dementia complex (n = 4) or with normal lumbar punctures (n = 3). CSF virus load correlated significantly with the number of infiltrating lymphocytes (r = .60, P < .001) but not with plasma virus load, the levels of beta2-microglobulin in the CSF, or the integrity of the blood-brain barrier. These data suggest significant intrathecal HIV-1 replication in patients with lymphocytic meningeal infections such as tuberculous and cryptococcal meningitis.

HIV-1 Subtype A, D, G, AG and Unclassified Sequences Identified in South Africa

HIV-1 subtype C accounts for the vast majority of infections in South Africa. However, increasingly non-C subtypes are being detected. Here we report 10 viruses that contain sequences that group with subtypes A, D, and G as well as CRF02_AG and 1 that could not be classified. Most of these individuals were from other countries in Africa. Some of these sequences were in combination with subtype C, possibly indicating local recombination events. Although there is no indication of endemic spread of these viruses, continued monitoring is warranted to track genetic changes, which may impact on diagnostic testing, therapeutic responses to antiretroviral therapies, and vaccine design.

Distribution of the human immunodeficiency virus coreceptors CXCR4 and CCR5 on leukocytes of persons with human immunodeficiency virus type 1 infection and pulmonary tuberculosis: Implications for pathogenesis

Expression of CXCR4 was significantly reduced from normal on all cell subsets of persons with pulmonary tuberculosis (TB group), with HIV-1 infection (HIV group), and those with both infections (HIV/TB group), except for on monocytes in the HIV group. The reductions were most notable in the two TB groups. Interestingly, the duration of antituberculosis treatment was significantly negatively correlated with the expression of CXCR4 on CD4+ and CD8+CD45RO+ cells, monocytes and NK cells, viral load, and proportions of CD38-expressing CD8+ lymphocytes, in HIV/TB patients. By contrast, CCR5 expression on most cell subsets analyzed was increased in all the disease groups, except for on monocytes in the two TB groups. There was no change in CCR5 expression on CD4+ cells when based on the disease groupings. However, higher proportions of CD4+CD45RA+ and CD8+ lymphocytes as well as B cells expressing CCR5 correlated with advancing HIV-1 disease, as did decreased proportions of CXCR4-expressing CD4+CD45RA+ cells.

The current epidemiology of hepatitis A infection in South Africa: implications for vaccination

Testing stored sera from various categories of individuals has shown that among the Black population hepatitis A virus (HAV) infection is universal and most adult Black subjects are immune. Infection probably occurs early in life, consistent with the epidemiological pattern seen in the developing world. By contrast, seroprevalence of HAV infection in adult White subjects increases with age, reflecting an epidemiological pattern seen in the developed world. White subjects working in a virological laboratory and White medical students had comparatively low seroprevalences of HAV infection and could therefore represent groups at risk. Hepatitis A vaccine is likely to be available in South Africa in the near future and could be offered to these groups. Pre-vaccination immunity screening would be a cost-effective strategy.

Interleukin-8 fails to induce human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines

This study addresses the role of interleukin (IL)‐8, a CXC‐chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus‐1 (HIV‐1)‐infected individuals, during the induction of HIV‐1 expression from latency and during cytokine‐mediated HIV‐1 up‐regulation. IL‐8 at the higher concentrations tested (≥ 100 ng/ml) was unable to induce HIV‐1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme‐linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV‐1 expression was only marginally reduced. HIV‐1 replication in acutely infected U937 cells was also significantly reduced by IL‐8. The potent up‐regulation of HIV‐1 expression in U1 cells by tumour necrosis factor‐α (TNF‐α) remained unaffected by the addition of IL‐8. HIV‐1 induction by IL‐1β, IL‐6 and TNF‐β, cytokines grouped here as intermediate HIV‐1 inducers, was suppressed by IL‐8 at concentrations of 1 and 10 ng/ml. However, IL‐8 at 100 ng/ml did not significantly alter the effect of IL‐1β, synergized with IL‐6 in enhancing, and marginally suppressed TNF‐β‐induced HIV‐1 expression. IL‐8 suppressed granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and enhanced interferon‐γ (IFN‐γ)‐induced HIV‐1 expression in a dose‐dependent manner. Pretreatment of U1 cells with IL‐8 did not alter the IL‐8‐mediated effects on cytokine‐induced HIV‐1 expression, suggesting that this chemokine exerts its effect at the time of HIV‐1 induction or at a postinduction stage. Furthermore, IL‐8 was itself induced by cytokines that up‐regulate HIV‐1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV‐1 and IL‐8. These results show that IL‐8, typically a non‐inducer, can differentially modulate HIV‐1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL‐8.

Human herpesvirus-8 antibodies and DNA in HIV-1 infected patients in South Africa

HIV-infected individuals with high levels of IgG antibodies against human herpesvirus-8 (HHV-8) are at increased risk of developing Kaposis sarcoma. The aim of this study was to measure the association between HHV-8 viraemia and IgG antibody responses (by immunofluorescence) in a group of 201 HIV-infected individuals attending outpatient clinics, 91 in-patients with AIDS and 87 HIV-infected patients admitted with Kaposis sarcoma. Compared to HIV-infected outpatients, the adjusted odds ratio in relation to Kaposis sarcoma was 15.4 (95% CI 4.4-54.2) in those with viraemia, 25.1 (95% CI 6.6-95.6) in those with a positive immunofluorescent signal and infinity (lower exact CI 33.6) in those with a high immunofluorescent signal (all P trend < 0.001). Among those without HHV-8 viraemia, 23% were IgG-positive, but only 5.5% had a high immunofluorescent signal. In those who were viraemic, 89.1% were IgG-positive, and 28.2% had a high immunofluorescent signal, suggesting viraemia is associated with high HHV-8 immunofluorescence IgG signal.

Interleukin-4 regulation of cytokine-induced HIV1 and interleukin-8 expression in promonocytic U1 cells is concentration-and cytokine-dependent

IL4 has been shown to differentially modulate HIV1 replication in primary cells of the monocyte/macrophage lineage. Its effects on chronic HIV1 infection, however, are unknown. To address IL4-mediated effects on promonocytic cells chronically infected with HIV1, U1 cells were incubated in the presence or absence of IL4 together with cytokines that are known to induce both HIV1 and IL8 expression. IL4 enhanced IL1 beta-induced HIV1 and IL8 expression in promonocytic U1 cells, whereas it suppressed their expression induced by cytokines IL6, GM-CSF and to a small extent, TNF alpha. IL4 suppressed IFN gamma-induced IL8 production with increasing IL4 concentration, while HIV1 p24 core antigen production was suppressed at low IL4 input (0.1 and 1 U/ml) but was substantially enhanced at a high IL4 input concentration (10 U/ml). Results showed that the immunosuppressive cytokine IL4 can behave variably in modulating HIV1 and IL8 expression, depending on both the inducing cytokine and the input concentration of IL4.

One year surveillance of HIV-1 infection in Johannesburg, South Africa

A sero-epidemiological surveillance study to monitor the prevalence of HIV-1 infection in Johannesburg, South Africa, was commenced in February 1988. The population selected for study were attenders at clinics for sexually transmitted diseases (STD) and at family planning (FP) clinics. In the 12 months of the study 6631 sera were tested. Of the STD attenders, 15 of 1224 black females (1.2%) and 21 of 2482 black males (0.8%) were positive. Of the 449 white males tested 49 were homosexual, amongst whom 10 (20.4%) were positive; in the heterosexual white male group 4 of 400 (1.0%) were positive. Of the FP clinic attenders, 4 of 1459 black females (0.3%) were positive. 68 of the 6631 sera tested were indeterminate for infection. No attenders were positive for HIV-2 infection. These data confirmed the entry of HIV infection into the black population in South Africa.

An analysis of indeterminate Western blot patterns of black African subjects

The significance of indeterminate Western blotting results was assessed by determining their distribution in attenders of sexually transmitted diseases (STD) and family planning (FP) clinics. As expected, it was found that the former had a highly significantly greater prevalence of HIV infection. Indeterminate results were not found more frequently in STD attenders refuting any association with sexual promiscuity. They were, however, found significantly more frequently amongst black compared to white subjects, but no difference was found between males and females. Indeterminate results appear to be a feature of black African sera and what the significance is, still remains to be elucidated.