Presence Of Human Immunodeficiency Virus Type 1 Research Articles

HIV-1 does not significantly influence Chlamydia trachomatis serovar L2 replication in vitro

Individuals with lymphogranuloma venereum (LGV), caused by Chlamydia trachomatis serovar L2, are commonly co-infected with human immunodeficiency virus type 1 (HIV-1), for reasons that remain unknown. One hypothesis is that a biological synergy exists between the two pathogens. We tested this by characterising for the first time in vitro C. trachomatis L2 replication in the presence of HIV-1. The human epithelial cell-line, MAGI P4R5 was infected with C. trachomatis L2 and HIV-1 (MN strain). Co-infected cultures contained fewer and larger chlamydial inclusions, but the inclusions did not contain morphologically aberrant organisms. C. trachomatis remained infectious in the presence of HIV-1 and showed neither an alteration in genome accumulation, nor in the acumulation of ompA, euo or unprocessed 16S rRNA transcripts. However, omcB was slightly elevated. Taken together, these data indicate that HIV-1 co-infection did not significantly alter C. trachomatis replication and the association between HIV-1 and LGV is likely due to other factors that require further investigation. The fewer, larger inclusions observed in co-infected cultures probably result from the fusion of multiple inclusions in HIV-1 induced syncytia and indicate that C. trachomatis-host-cell interactions continue to function, despite considerable host-cell re-modelling.

Inefficient fusion due to a lack of attachment receptor/co-receptor restricts productive human immunodeficiency virus type 1 infection in human hepatoma Huh7.5 cells

Since the widespread use of the highly active antiretroviral therapy, the incidence of liver disease has increased to become a leading cause of death among human immunodeficiency virus type 1 (HIV-1)-infected individuals. It can be proposed that the ability of HIV-1 to infect hepatocytes could influence liver diseases. Although the presence of HIV-1 was identified in hepatocytes from HIV-1 seropositive patients, the susceptibility of hepatocytes to HIV-1 infection in vitro remains controversial. We present evidence here that human hepatoma cells are not productively infected with CD4-dependent HIV-1 strains because of inefficient fusion related to an absence of cell surface CD4 and CXCR4. However, these cells display an increased susceptibility to infection with a CD4-independent viral isolate through an interaction with galactosyl ceramide, an alternate receptor for HIV-1. This study provides further understanding of the susceptibility of human hepatocytes to HIV-1 infection. However, in vivo investigations are recommended to consolidate these data.

Cross-Interaction between JC Virus Agnoprotein and Human Immunodeficiency Virus Type 1 (HIV-1) Tat Modulates Transcription of the HIV-1 Long Terminal Repeat in Glial Cells

The human polyomavirus JC virus (JCV) is the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), which is commonly seen in AIDS patients. The bicistronic viral RNA, which is transcribed at the late phase of infection, is responsible for expressing the viral capsid proteins and a small regulatory protein, agnoprotein. Immunohistochemical analysis of brain tissue from subjects with AIDS/PML revealed colocalization of the human immunodeficiency virus type 1 (HIV-1) transactivator, Tat, and JCV agnoprotein in nucleus and cytoplasm of "bizarre" astrocytes. In accord with this observation, we detected the copresence of agnoprotein and Tat in human astrocytes upon infection with JCV and HIV-1 or in astrocytic cells expressing these proteins after transfection. Interestingly, results from infection of human astrocytes with HIV-1 and JCV showed a decrease in the level of HIV-1 replication in cells that are coinfected with JCV. Conversely, a slight increase in the level of JCV replication was observed in the presence of HIV-1. The copresence of JCV and HIV-1 in astrocytes prompted us to investigate the possible cross-interaction of agnoprotein with Tat and its impact on HIV-1 gene transcription. Our results demonstrate that agnoprotein through its N-terminal domain associates with Tat and the interaction causes the suppression of Tat-mediated enhancement of HIV-1 promoter activity in these cells. Results from RNA and protein binding assays showed that agnoprotein can inhibit the association of Tat with its target RNA sequence, TAR, and with cyclin T1. Furthermore, agnoprotein is able to interfere with cross-interaction of Tat with the p65 subunit of NF-kappaB and Sp1, whose functions are critical for Tat activation of the long terminal repeat. These observations unravel a new pathway for the molecular interaction of these two viruses in biologically relevant cells in the brains of AIDS/PML patients.

Transmission of human immunodeficiency virus type 1 through breast-feeding: how can it be prevented?

One-third to two-thirds of maternal transmission of human immunodeficiency virus type 1 (HIV-1) infection to breast-fed infants can be attributed to ingestion of breast milk. The presence of HIV-1 as cell-free and as cell-associated virus in milk has been documented. Several substances in breast milk may be protective against transmission, including maternal anti-HIV antibodies, vitamin A, lactoferrin, and secretory leukocyte protease inhibitor. The portal of virus entry in the infant's gastrointestinal tract is unknown but may involve breaches in mucosal surfaces, transport across M cells, or direct infection of other epithelial cells, such as enterocytes. Timing of transmission of HIV-1 during lactation should be further clarified. An early rebound of plasma viremia after withdrawal of antiretrovirals was recently detected. This rebound may reduce the benefit of antiretroviral prophylaxis when women breast-feed their infants. Interventions should be viewed from the public health perspective of risks of infant morbidity and mortality associated with breast-feeding versus risks from formula-feeding.

Human immunodeficiency virus type 1–serodiscordant couples can bear healthy children after undergoing intrauterine insemination

Objective: To use semen from men who were seropositive for human immunodeficiency virus type 1 (HIV-1) to inseminate their partners without infecting them. Design: Prospective study. Setting: Private practice. Patient(s): Sixty-three HIV-1–seropositive men and their HIV-1–seronegative female partners. Intervention(s): The men provided 107 semen samples that were prepared with the use of the Percoll and swim-up techniques. The presence of HIV-1 was determined in the fraction of motile spermatozoa obtained after washing. If HIV-1 was not detected, IUI was performed in stimulated cycles. Main Outcome Measure(s): Human immunodeficiency virus type 1 RNA and DNA were detected with the use of the polymerase chain reaction technique modified for spermatozoa. Result(s): One hundred seven semen samples were washed. Human immunodeficiency virus type 1 was not detected in 101 samples (94.4%) and was detected in 6 samples (5.6%). In the latter cases, IUI was not performed. One hundred one IUI procedures were performed in 63 women. Thirty-one pregnancies resulted, for a pregnancy rate of 30.7% per cycle and 49.2% per inseminated woman. Thirty-seven healthy children were born. The results of tests for the detection of HIV-1 and antibodies to HIV-1 in the inseminated women were negative. Conclusion(s): On the basis of these results, testing for HIV-1 with the use of the polymerase chain reaction technique on the semen fraction obtained after washing appears to prevent infection in the inseminated woman. This method makes it possible to help HIV-1–seropositive men to have children without infecting their female partners.

Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) infection is known to increase the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma. Parallels with other causes of immunodeficiency suggest a possible effect of HIV-1 on additional cancers. This study was designed to determine the types and rates of cancers occurring in excess in the presence of HIV-1 infection. We examined cancer incidence in a population-based open cohort with a high prevalence of HIV-1 infection. The study population was never-married men aged 25-54 years who resided in San Francisco, Calif., of whom an estimated 20,000 (24%) were HIV-1 seropositive as of late 1984. Cancer registration data covering 1,390,000 person-years of observation of these men from 1973 through 1990 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Standardized incidence rates and ratios of observed to expected cases (based on rates in the pre-acquired immunodeficiency syndrome [pre-AIDS] period [i.e., 1973-1979]) were calculated for cancers classified by site and by cell type. The incidence of Kaposi's sarcoma in never-married men plateaued in 1988-1990 at 0.5% per year. The incidence of non-Hodgkin's lymphoma increased 20-fold between 1973-1979 and 1988-1990; increases were most pronounced in tumors of higher grade histology and extranodal (especially central nervous system) primary sites. The incidence of Burkitt's and Burkitt-like tumors peaked in 1985-1987, whereas that of large cell diffuse and immunoblastic lymphomas increased throughout the study period. The incidence of Hodgkin's disease was 2.0 (95% confidence interval [CI] = 1.3-3.0) times expected in 1988-1990. The incidence of anal cancer was 9.9 (95% CI = 4.5-18.7) times expected in 1973-1979 and 10.1 (95% CI = 5.0-18.0) times expected in 1988-1990. Ratios of observed to expected cancers of most other sites were 2.0 or less; the ratio of leiomyosarcomas (at any site) was 2.5 (95% CI = 0.5-7.4). As the HIV-1 epidemic has progressed, the increases in AIDS-related Kaposi's sarcoma, Burkitt's tumor, and other non-Hodgkin's lymphoma have followed different patterns. The effect of HIV-1 on other cancers has been nondetectable. In particular, HIV-1 is not related to the increased risk of anal cancer in homosexual men, which antedated the AIDS epidemic. These data suggest that the etiologic mechanisms of HIV-1-related malignancy differ for specific cancers and do not globally increase cancer risk. Control of HIV-1-related cancer remains an unsolved challenge in the management of HIV-1 infection.

The effect of human immunodeficiency virus type-1 on the infectiousness of tuberculosis

Setting: Developing country tertiary referral hospital plus catchment community. Objective: To determine the infectiousness of culture-confirmed pulmonary tuberculosis in patients infected with Human Immunodeficiency Virus type-1 (HIV-1). Design: Comparison of the incidence of tuberculosis and the prevalence of tuberculin skin test positivity among the household contacts of both HIV-1 positive and negative cases with pulmonary tuberculosis. Results: Of 255 contacts of HIV-1 negative index cases, 2 were HIV-1 positive and of 102 contacts of HIV-1 positive index cases, 14 were HIV-1 positive (odds ratio (OR) = 20.0 95% Confidence Interval (CI) 4.4−193). 21 cases of tuberculosis were diagnosed among contacts, of whom 3 were HIV-1 positive. The overall unadjusted OR for tuberculosis among contacts of HIV-1 positive index cases was 1.6 (95% CI 0.6−4.3) compared to contacts of HIV-1 negative index cases. Amongst HIV-1 negative contacts alone the OR was 1.5 (95% CI 0.4−4.4). In this group the best predictors of tuberculosis among contacts were female sex of the index case (OR = 3.4 95% CI 1.1−12), sharing the same bed as the index case (OR = 2.6 95% CI 0.9−7.4), and contact's age less than 5 years (OR = 3.3 95% CI 1.1−9.5). HIV-1 positive contacts were more likely to develop tuberculosis than HIV-1 negative contacts (OR = 4.1 95% CI 0.7−17). Tuberculin skin test positivity rates were the same among the HIV-1 negative contacts of HIV-1 positive and negative index cases (OR = 1.1 CI 0.7−1.6). Conclusions: HIV-1 associated pulmonary tuberculosis is not more infectious than tuberculosis alone. The presence of HIV-1 in a community does not mandate a change in the management of contacts of patients with pulmonary tuberculosis.

Virologic Markers of Human Immunodeficiency Virus Type 1 in Cerebrospinal Fluid

As part of a longitudinal study, 265 cerebrospinal fluid (CSF) specimens from 204 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects and 43 seronegative controls were evaluated. Of the 204 seropositive persons, 78 (38%) had > or = 1 CSF culture positive for HIV-1; the probability of being culture positive increased as the number of CSF samples obtained increased (P = .0018). Significantly correlated with culture positivity were elevations in CSF protein level (P = .014) and CSF white blood cell count (P = .001). Virus was more readily cultured from clarified CSF (89%, 42/47) than from the cellular fraction (30%, 14/47; P < .00001). Amplification of HIV-1 DNA by polymerase chain reaction (PCR) from 25 seropositive persons was positive in 9 (82%) of 11 culture-positive and in 4 (29%) of 14 culture-negative specimens, while amplification of viral RNA detected all 11 culture-positive and 9 (64%) of the 14 culture-negative CSF specimens. These data support the hypothesis that the development of HIV-1-associated neurocognitive disorders are not dependent solely on the presence of HIV-1 within the central nervous system.

Spectrum of human immunodeficiency virus-associated neocortical damage.

A spectrum of neurocognitive defects, termed human immunodeficiency virus type 1 (HIV-1)-associated cognitive/motor complex, has been described in patients with acquired immunodeficiency syndrome (AIDS). AIDS dementia complex (ADC) is a severe form of this disease seen in 20 to 30% of terminally ill patients. The etiology of this complex is distinct from commonly observed opportunistic infections seen in brains of patients with AIDS and has been attributed to HIV infection within the brain. At autopsy, the brains of patients with ADC contain numerous HIV-infected macrophages/microglia with prominent subcortical damage, together termed HIV encephalitis. We retrospectively analyzed all 107 brains from a three-year period (1988-1990) of AIDS autopsies using immunocytochemistry to detect HIV. Rather than breaking into distinct groups of HIV encephalitis versus non-HIV encephalitis, the specimens revealed a spectrum of severity of HIV infection. Although only 16% of the brains showed the histological hallmarks of HIV encephalitis, more than 50% of the autopsies showed moderate to severe HIV infection. In a subset of 23 AIDS autopsies during which short postmortem times and absence of significant opportunistic infection permitted quantitative analysis of dendritic and synaptic complexities, we identified a strong correlation between neocortical dendritic and presynaptic damage and abundance of HIV envelope protein in the neocortical gray and deep white matter. This correlation suggests that the presence of HIV-1 in the neocortex may be responsible by direct or indirect mechanisms for dendritic and synaptic damage.

Confirmation and differentiation of antibodies to human immunodeficiency virus 1 and 2 with a strip-based assay including recombinant antigens and synthetic peptides

We evaluated the use of the INNO-LIA HIV-1/HIV-2 Ab test (LIA HIV; Innogenetics) for the confirmation of antibodies to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The test includes three recombinant HIV-1 proteins: p24 (gag), p17 (gag), and endonuclease (p31; pol), in combination with two synthetic peptides derived from the env gene of HIV-1 and one synthetic peptide selected from the env gene of HIV-2. Analysis of 450 sera from blood donors, 220 sera from patients with non-HIV pathology, and 28 Western blot (WB) p24-only reactive sera revealed no false-positive results, and the rate of indeterminate results was substantially lower than that with WB. Testing of 334 WB-confirmed HIV antibody-positive sera (309 HIV-1; 25 HIV-2) revealed no false-negative results. In two of seven seroconversion panels tested, LIA HIV detected the presence of HIV antibodies before WB did. In the other five panels, LIA HIV and WB confirmed the presence of HIV antibodies in the same sample. The LIA HIV assay therefore appears well suited for routine confirmation of the presence of HIV-1 and HIV-2 antibodies.

Quantitative Detection of Brain Aberrations in Human Immunodeficiency Virus Type I-Infected Individuals by Magnetic Resonance Imaging

The brains of 65 individuals with antibodies to human immunodeficiency virus type 1 (HIV-1), 20 HIV-1 seronegative homosexual men, and 75 heterosexual controls were examined by a quantitative magnetic resonance imaging technique. A white matter aberration was detected most frequently in patients with AIDS-related complex (ARC) or AIDS, but also in asymptomatic HIV-1 seropositive persons and in HIV-1 seronegative homosexual men, of whom two of three tested were reactive for HIV-1 DNA by polymerase chain reaction. The aberration was not found in the control group. Brain atrophy was mainly confined to patients with ARC or AIDS. The brain lesions correlated with the presence of HIV-1 in cerebrospinal fluid and with elevated levels of beta 2-microglobulin and neopterin. The most pronounced brain aberrations were in patients with AIDS-dementia complex. These findings indicate that brain aberrations may occur in persons in the early stages of HIV-1 infection, although to no greater extent than in HIV-1 seronegative homosexual men. The occurrence of pronounced brain lesions seems to be associated with the presence of an advanced immunodeficiency.

HIV-1 Infection of Lung Alveolar Fibroblasts and Macrophages in Humans

We have studied the infected cell populations in the lungs of four human immunodeficiency virus type 1 (HIV-1) seropositive patients suffering from lymphocytic alveolitis or lymphocytic interstitial pneumonitis. Adherent cells were obtained by bronchoalveolar lavage (BAL) and were analyzed by various technical approaches. The cells considered here were alveolar macrophages and fibroblasts, and could be clearly identified morphologically and by the expression of specific cell-surface markers using monoclonal antibodies. The presence of HIV-1 in both of these cell types was established by serological, virological, and molecular procedures. Our results show that alveolar macrophages and fibroblasts are naturally infected in the lungs of HIV+ patients. Both cell types express the CD4 receptor molecule, in contrast to skin fibroblasts which are negative. Alveolar macrophages and fibroblasts thus may act as eventual HIV-1 reservoirs in vivo, and are probably involved in the induction of inflammatory reactions because they are targets for CD8 cytotoxic T lymphocytes (CTL).

Absence of Infectious HIV-1 in the Urine of Seropositive Viremic Subjects

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.

WHAT DO WESTERN BLOT INDETERMINATE PATTERNS FOR HUMAN IMMUNODEFICIENCY VIRUS MEAN IN EIA-NEGATIVE BLOOD DONORS?

To investigate the specificity of western blot indeterminate (WBi) patterns for antibodies to the human immunodeficiency virus type 1 (HIV-1), 100 enzyme immunoassay (EIA) negative donors from whom prospectively obtained recipient sera were available were tested by WB. 20 were WBi, with p24 being the predominant (70%) and generally the only band. Among recipients of WBi blood, 36% were WBi in their 6 month post-transfusion sample, but so were 42% of a control population that had received only WB-negative blood. When serial samples from recipients with a WBi pattern were tested on two occasions, only 35% of results were reproducible. No recipient of WBi blood became EIA positive, true positive for WB, positive for HIV-1 antigen, or positive for EIA reactivity against recombinant p24 or gp41. The polymerase chain reaction was negative for gag and env HIV-1 sequences in all donors and recipients. Thus WBi patterns are exceedingly common in randomly selected donors and recipients and such patterns do not correlate with the presence of HIV-1 or the transmission of HIV-1 from donor to recipient.