HIV-infected AIDS Patients Research Articles

Exploration of the Nursing Intervention of Positive Psychological Theory on HIV Infected AIDS Patients

Exploration of the Nursing Intervention of Positive Psychological Theory on HIV Infected AIDS Patients

An Important Role for CD4+ T Cells in Adaptive Immunity to Toxoplasma gondii in Mice Lacking the Transcription Factor Batf3.

Immunity to Toxoplasma gondii at early stages of infection in C57BL/6 mice depends on gamma interferon (IFN-γ) production by NK cells, while at later stages it is primarily mediated by CD8 T cells. We decided to explore the requirement for CD4 T cells during T. gondii infection in Batf3-/- mice, which lack CD8α+ dendritic cells (DCs) that are necessary for cross-presentation of cell-associated antigens to CD8 T cells. We show that in this immunodeficient background on a BALB/c background, CD4 T cells become important effector cells and are able to protect Batf3-/- mice from infection with the avirulent strain RHΔku80Δrop5 Independently of the initial NK cell activation, CD4 T cells in wild-type and Batf3-/- mice were the major source of IFN-γ. Importantly, memory CD4 T cells were sufficient to provide protective immunity following transfer into Batf3-/- mice and secondary challenge with the virulent RHΔku80 strain. Collectively, these results show that under situations where CD8 cell responses are impaired, CD4 T cells provide an important alternative immune response to T. gondiiIMPORTANCEToxoplasma gondii is a widespread parasite of animals that causes zoonotic infections in humans. Although healthy individuals generally control the infection with only moderate symptoms, it causes serious illness in newborns and those with compromised immune systems such as HIV-infected AIDS patients. Because rodents are natural hosts for T. gondii, laboratory mice provide an excellent model for studying immune responses. Here, we used a combination of an attenuated mutant strain of the parasite that effectively vaccinates mice, with a defect in a transcriptional factor that impairs a critical subset of dendritic cells, to studying the immune response to infection. The findings reveal that in BALB/c mice, CD4 memory T cells play a dominant role in producing IFN-γ needed to control chronic infection. Hence, BALB/c mice may provide a more appropriate model for declining immunity seen in HIV-AIDS patients where loss of CD4 cells is associated with emergence of opportunistic infections.

Cryptococcus gattii Comparative Genomics and Transcriptomics: A NIH/NIAID White Paper

Cryptococcus gattii is an emerging global pathogen. Recent reports suggest that C. gattii cryptococcosis is more common in immunocompetent as well as HIV-infected AIDS patients than earlier estimated. An ongoing outbreak of C. gattii in Vancouver, Canada, and the US Pacific Northwest has heightened public health awareness in North America. We have few clues as to what causes emergence or re-emergence of highly pathogenic strains, why C. gattii split up from its sibling pathogen C. neoformans, why it thrives in trees instead, and why immunocompetent individuals are vulnerable to this pathogen? C. gattii comprises of four distinct lineages, but the information on the genome of C. gattii is inadequate and unrepresentative as it is limited to two strains, R265 and WM276, which are MATα, serotype B, genotype VGII/VGI from Canada and Australia, respectively. There is a wide gap in knowledge about the genomes of VGIII and VGIV strains, serotype C strains, and MATa strains. The geographical representation is inadequate in the absence of strains from California, South America, Asia, and Africa. Additional obstacles to work with this pathogen are the following: (a) complex molecular typing schemes and (b) lack of functional genomics analyses. We propose to complete genome sequencing of 12 reference strains by next-generation sequencing technology and to map their transcriptomes by RNA-Seq technology. This effort would lead to new resources for the scientific community including (1) insight from additional C. gattii genomes to anchor future research studies, (2) validation of single-nucleotide polymorphisms (SNPs) for molecular typing to improve epidemiology studies, and (3) transcript analyses from strains under relevant pathogenic and non-pathogenic conditions to accelerate the discovery of proteins for diagnostics, drug targets, and vaccines.

Epidemiology of adenovirus type 5 neutralizing antibodies in healthy people and AIDS patients in Guangzhou, southern China

Recombinant adenovirus serotype 5 (Ad5) viruses have been extensively explored as vectors for vaccination or gene therapy. However, one major obstacle to their clinical application is the high prevalence of preexisting anti-Ad5 immunity resulting from natural infection. It has been reported that there are geographic variations in the prevalence of natural adenovirus infection. In the present study, we investigated the seroprevalence of Ad5 in Guangzhou, southern China by measuring the Ad5 neutralizing antibodies in blood samples collected from several sites. The seroprevalence was 77.34% in the general healthy population. The seroprevalence and antibody titers increased with age, with the older population (41-72 years old) having the highest seropositivity (84.8%) and percentage (54.4%) of high Ad5 neutralizing antibody titers (>1000). The dynamics of Ad5 neutralizing antibodies were stable and persistent over the course of eight months. Furthermore, the seroprevalence of Ad5 in the HIV-infected AIDS patients was investigated and there was no significant difference from the general healthy population. Our survey provides useful insights for the future development of Ad5-based vaccination and gene therapy.

Decreased Levels of Circulating IL-21 in HIV-Infected AIDS Patients: Correlation with CD4+ T-Cell Counts

IL-21 is a relatively newly discovered multifunctional and pleiotropic cytokine. It is produced primarily by CD4(+) T cells, the principal targets of the virus, and therefore this cytokine has special relevance to HIV infection. Here we show for the first time that serum levels of this cytokine are significantly reduced in HIV-infected AIDS patients and correlate significantly with their CD4(+) T-cell counts. These data suggest that the cytokine levels could act as a valuable biomarker for the progression of AIDS.

Contribution of platelet activation to plasma IL-18 concentrations in HIV-infected AIDS patients

Contribution of platelet activation to plasma IL-18 concentrations in HIV-infected AIDS patients

IL-15 and HIV Infection: Lessons for Immunotherapy and Vaccination

IL-15 is a pleiotropic and multifunctional cytokine that has a diverse array of distinct biological effects in the body. It plays a crucial role in host defense from viral and non-viral intracellular pathogens. The cytokine is essential for the development and differentiation of NK cells and for homeostatic expansion of CD8+ memory T cells, NKT cells and certain subsets of intestinal intra-epithelial lymphocytes (iIEL). It acts as a survival factor and inhibits spontaneous apoptosis in T, B and NK cells by increasing expression of different anti-apoptotic proteins. Several studies have shown that IL-15 production is compromised in HIV-infected AIDS patients and exogenous IL-15 drastically enhances functions of immune cells from these patients. Considering these distinct immune enhancing effects, relative safety in animal models, and minimal effects on HIV replication, IL-15 may represent a better cytokine for immune reconstitution in these patients. Furthermore, IL-15 may also act as a better adjuvant in eliciting antiviral immunity in anti-HIV vaccine strategies.

Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients

Natural interferon-alpha producing cells (IPCs) are a newly characterized blood cell type, which is the major source of type I interferons in antiviral innate immune responses. The relationship between the number of circulating IPCs, HIV disease progression, and the occurrence of HIV-related complications was investigated. The study of 25 healthy donors and 54 HIV-infected subjects demonstrated a direct correlation between blood IPC number, interferon-alpha production, and clinical state of HIV-infected subjects. Asymptomatic long-term survivors had increased IPC number and function relative to uninfected controls and infected individuals with progressive disease. IPC numbers were markedly reduced in AIDS patients developing opportunistic infections and cancer. A negative correlation was found between the IPC number in the blood and the HIV viral load, suggesting that IPCs are important in controlling HIV replication. This study provides the first evidence that IPCs are being affected during the course of HIV infection and suggests that these cells can play a vital role in the protection against opportunistic pathogens and cancer. (Blood. 2001;98:906-912)

Differential gene expression in B-cell non-Hodgkin's lymphoma of SIV-infected monkey.

Infection with SIVmac251 in some rhesus monkeys (Macaca mulatta) leads to B-cell non-Hodgkin's lymphomas (B-NHL) clinically similar to that of HIV-infected AIDS patients. To further characterize the SIV-associated B-NHL we have generated genetic profiles of malignant cells by subtractive hybridization and Northern blot analysis. We have analyzed 21 clones of a subtracted cDNA library corresponding to overexpressed genes in diffuse large B-cell (DLBCL) SIV-associated monkey lymphoma. Eight of these clones represent a sequence homologous to an abundant transcript from KG-1 cells originally established from a human myelogenous leukemia. The protein encoded has a 60% similarity to a hypothetical glycine-rich transmembrane signal protein of Caenorhabditis elegans and 25% similarity to the ret finger protein. The other cDNA clones contained sequences of the serum amyloid A gene (SAA), the alpha1-acid glycoprotein gene (AGP), the ribosomal protein S3a (RPS3a) and L8 (RPL8) genes, the interferon-inducible gene (INF-ind), the metastasin gene (mts1), and the NADH dehydrogenase I gene (ND-I). The remaining cDNA clones consisted of yet unknown sequences. In addition, we detected an up-regulation of the cytochrome c oxidase II gene (COX-II), the ND-IV gene, and the SET oncogene by Northern blot hybridization in three SIV-associated NHLs of different histomorphological classification. All these genes have not previously been found to be overexpressed in B-NHL.

Protective effects of hochu-ekki-to, a Chinese traditional herbal medicine against murine cytomegalovirus infection.

The innate immunity against murine cytomegalovirus (MCMV) at the early phase of infection is mediated by NK cells and macrophages. We studied the effects of hochu-ekki-to (HET), a traditional Chinese herbal medicine, on the regulation of innate immunity mediated by NK cells and macrophages. We found the oral administration of HET to increase both the number of leukocytes in the spleen and liver and the splenic NK cell cytotoxicity associated with the increased induction of serum IFN-alpha/beta after an MCMV infection but it had no effect on liver NK cells. However, no differences were found in the serum IL-12, IFN-gamma, TNF-alpha and nitric oxide (NO) production in the culture of macrophages between the HET- and PBS-treated mice on day 2 after MCMV infection. In addition, HET-treated splenic and peritoneal macrophages were found to show a higher intrinsic resistance against in vitro MCMV infection than that of PBS-treated mice. Therefore, the HET-induced effects on NK cells and macrophages selectively reduced the viral load in the spleen but not in the liver at an early phase of MCMV infection. HET may thus be useful in the treatment of human cytomegalovirus infection which commonly occurs in HIV-infected AIDS patients.