Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chimeric simian/human immunodeficiency virus (SHIV) consists of the env, vpu, tat, and rev genes of human immunodeficiency virus type 1 (HIV-1) on a background of simian immunodeficiency virus (SIV). We derived a SHIV that caused CD4+ cell loss and AIDS in pig-tailed macaques (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L. J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996) and used a cell-free stock of this virus (SHIV(KU-1)) to inoculate macaques by the intravaginal route. Macaques developed high virus burdens and severe loss of CD4+ cells within 1 month, even when inoculated with only a single animal infectious dose of the virus by the intravaginal route. The infection was characterized by a burst of virus replication that peaked during the first week following intravenous inoculation and a week later in the intravaginally inoculated animals. Intravaginally inoculated animals died within 6 months, with CD4+ counts of <30/microl in peripheral blood, anemia, weight loss, and opportunistic infections (malaria, toxoplasmosis, cryptosporidiosis, and Pneumocystis carinii pneumonia). To evaluate the kinetics of virus spread, we inoculated macaques intravaginally and euthanized them after 2, 4, 7, and 15 days postinoculation. In situ hybridization and immunocytochemistry revealed cells expressing viral RNA and protein in the vagina, uterus, and pelvic and mesenteric lymph nodes in the macaque euthanized on day 2. By day 4, virus-infected cells had disseminated to the spleen and thymus, and by day 15, global elimination of CD4+ T cells was in full progress. Kinetics of viral replication and CD4+ loss were similar in an animal inoculated with pathogenic SHIV orally. This provides a sexual-transmission model of human AIDS that can be used to study the pathogenesis of mucosal infection and to evaluate the efficacy of vaccines and drugs directed against HIV-1.
 ...
PMID:Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS. 909 79

The mode of heterosexual transmission of human immunodeficiency virus (HIV) is not yet understood. The semen of HIV-infected men contains free virus and infected cells, and it is not known which of these is more important for sexual transmission of the virus to women. Some investigators have presented in vitro studies supporting a cellular mode of transmission of HIV and have suggested that infected lymphoid cells may act as the primary source of infection. This has become known as the "Trojan Horse" hypothesis. In vivo demonstrations of such events are lacking and are not likely to be forthcoming using human subjects. To investigate the ability of normal lymphoid cells to invade the cervicovaginal mucosa in an experimental animal, we stained C3H/He (H-2Kk) mouse peritoneal lymphoid cells with bisbenzimide, a vital fluorescent DNA-binding dye, and inoculated the cells atraumatically into the vaginas of progestin-treated, BALB/c (H-2Kd) recipient mice. Donor cells were identified in recipient tissues by their bisbenzimide-fluorescent nuclei and by fluorescein staining of the membrane antigen, H-2Kk. Donor lymphoid cells were observed in histological sections of recipient cervicovaginal mucosa and also in the iliac lymph nodes of 34 of 36 recipient mice 24 h after inoculation into the vagina. The number of donor cells in the iliac lymph nodes was 8.6 +/- 1.4 (mean +/- SEM) cells per mouse with a range of 0-35 cells per mouse. Approximately 28% of the donor lymphoid cells in recipient lymph nodes expressed CD4, which in humans is the receptor for HIV. We did not detect F4/80, a marker of mature mouse macrophages in the donor cell population, on any of the migrating cells in recipient lymph nodes. However, this negative result is equivocal, because the marker might be down-regulated after transfer or the migrating macrophages might be difficult to dissociate from the recipient lymph node tissue. These observations in mice support the suggestion that HIV-containing lymphoid cells in the semen of infected men may invade the cervicovaginal mucosa after sexual intercourse and deliver the virus to a woman's internal environment. However, both the donor cells and the recipient reproductive tract of the mice in the present study differed in significant respects from their counterparts in humans that might be involved in heterosexual HIV transmission. Further studies are needed to determine whether this possible mode of virus transmission is mainly responsible for heterosexual transmission of HIV in humans.
 ...
PMID:Migration of foreign lymphocytes from the mouse vagina into the cervicovaginal mucosa and to the iliac lymph nodes. 911 58

In clinical trials, nonoxynol-9 has been shown to protect against the transmission of sexually transmitted pathogens. Conversely, there are concerns that frequent use may lead to vaginal irritation and thus increase the risk of transmission of sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV). Nonoxynol-9 is available as a foam, cream, gel, film, and suppository. These routes of administration differ from each other in their total unit dose, ability to irritate genital tissues, rates of dissolution, and ability to coat the vagina. To determine a method for collection and recovery of vaginally administered nonoxynol-9, and thereby facilitate research on the role of nonoxynol-9 in the prevention of HIV, a feasibility study was performed in 11 healthy, premenopausal US women. Also investigated was whether nonoxynol-9 could be quantitated in vaginal lavage fluid obtained 2 hours after instillation of 100 mg of nonoxynol-9 foam (Delfen). The quantity of nonoxynol-9 collected at this time ranged from 10.8-67.8 mg (mean, 35.4 mg), corresponding to a recovery rate of 11-70% of the original dose. Although further studies are needed to optimize methods for nonoxynol-9 recovery from the vagina, this study suggests it is feasible to quantitate nonoxynol-9 after single-dose vaginal administration.
 ...
PMID:Quantitation of vaginally administered nonoxynol-9 in premenopausal women. 917 59

A report that genetic subtype E human immunodeficiency virus type 1 (HIV-1) strains display a preferential tropism for Langerhans cells (epidermal dendritic cells [DCs]) compared to genetic subtype B strains suggested a possible explanation for the rapid heterosexual spread of subtype E strains in Thailand (L. E. Soto-Ramirez et al., Science 271:1291-1293, 1996). In an independent system, we applied subtype E and B isolates to skin leukocytes, since skin is a relevant model for the histologically comparable surfaces of the vagina and ectocervix. Isolates of both HIV-1 subtypes infected DC-T-cell mixtures, and no subtype-specific pattern of infection was observed. Purified DCs did not support the replication of strains of either subtype B or E. Our findings do not support the conclusion that subtype E strains have a preferential tropism for DCs, suggesting that other explanations for the rapid heterosexual spread of subtype E strains in Asia should be considered.
 ...
PMID:Human immunodeficiency virus type 1 strains of subtypes B and E replicate in cutaneous dendritic cell-T-cell mixtures without displaying subtype-specific tropism. 931 95

Cynomolgus monkeys (Macaca fascicularis) were immunized by intravaginal administration of live recombinant Streptococcus gordonii. The vaccine strains of S. gordonii expressed the V3 domain of the gpl20 of human immunodeficiency virus type 1 (HIV-1), and the E7 protein of human papillomavirus type 16 (HPV 16). Multiple inocula of recombinant bacteria were used, since S. gordonii could persist for no longer than 3 days in the monkey vagina. Vaginal immunization was found to induce a local and systemic immune response specific for the heterologous antigen expressed by the bacteria. This antigen-specific immune response consisted of vaginal IgA, serum IgG, and a T-cell proliferative response measured on PBMCs. Vaginal IgG and serum IgA were not detected.
 ...
PMID:Vaginal immunization of Cynomolgus monkeys with Streptococcus gordonii expressing HIV-1 and HPV 16 antigens. 949 3

Significant progress has been made in understanding the biology of heterosexual transmission of HIV by utilizing the simian immunodeficiency virus (SIV)/rhesus monkey animal model. Our previous studies have shown that SIV-infected cells within the stratified squamous epithelium of the vagina have a dendritic morphology. However, the type of cell infected was not conclusively determined. The purpose of the present study was to immunophenotype the SIV-infected cells in the lower reproductive tract and genital lymph nodes of the female rhesus monkey. Vagina, cervix, and iliac lymph node from eight chronically SIV-infected adult female monkeys were examined for this study. None of the animals had histologic evidence of opportunistic infections or genital tract pathogens other than SIV. Combined in situ hybridization and immunohistochemistry were used to detect SIV RNA and to determine the immunophenotype of SIV-infected cells in tissue sections and cytospin preparations of cells from the tissues. We now show that SIV-infected cells were most common in iliac lymph node and that the majority of infected cells in the lymph node were T lymphocytes. SIV-infected macrophages, Langerhans' cells, and dendritic cells were also found in the lymph node. SIV-infected cells were found within the epithelium and lamina propria of the vagina. Although most of the infected cells were T cells, a significant proportion (approximately 40%) of the SIV-infected cells in cytospin preparations from explant cultures of vagina and cervix were Langerhans' cells. SIV-infected T cells in the lower genital tract were commonly associated with focal mononuclear cell infiltrates. SIV-infected macrophages were rarely found in the genital tract. The present study provides the first direct demonstration that Langerhans' cells and dendritic cells in the genital tract and lymph nodes are infected with SIV in vivo. Thus, dendritic cells, in general, and Langerhans' cells, in particular, are important reservoirs for HIV/SIV replication in vivo.
 ...
PMID:Immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys. 984 Jun 10

We have evaluated the in vivo distribution of the major human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV/SIV coreceptors, reaffirming that these cells are the major targets of HIV/SIV infection in vivo. In lymphoid tissues such as the lymph node and the thymus, approximately 1 to 10% of the T lymphocytes and macrophages are coreceptor positive. However, coreceptor expression was not detected on follicular dendritic cells (FDC) in lymph nodes, suggesting that the ability of FDC to trap extracellular virions is unlikely to be mediated by a coreceptor-specific mechanism. In the thymus, a large number of immature and mature T lymphocytes express CXCR4, which may render these cells susceptible to infection by syncytium-inducing viral variants that use this coreceptor for entry. In addition, various degrees of coreceptor expression are found among different tissues and also among different cells within the same tissues. Coreceptor-positive cells are more frequently identified in the colon than in the rectum and more frequently identified in the cervix than in the vagina, suggesting that the expression levels of coreceptors are differentially regulated at different anatomic sites. Furthermore, extremely high levels of CXCR4 and CCR3 expression are found on the neurons from both the central and peripheral nervous systems. These findings may be helpful in understanding certain aspects of HIV and SIV pathogenesis and transmission.
 ...
PMID:In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5. 957 73

The relationship between human immunodeficiency virus type 1 (HIV-1) viral RNA and proviral DNA load in vagina and cervix and that found in the plasma and peripheral blood mononuclear cells (PBMC) was investigated in 28 HIV-1-infected women. Of the patients, 64% had > or = 1 HIV-1 RNA-positive genital sample, while 71% had > or = 1 DNA-positive sample. The higher the cervical HIV load, the more widespread was the virus in the genital tract. A strong correlation was found between viral RNA load in plasma and the genital tract, whereas the association between proviral DNA load in PBMC and the genital tract was less evident. Cervical HIV-1 DNA correlated with a viral RNA load > or = 50,000 copies/mL. Cervical HIV-1 RNA levels ranged from 10% to 100% of the plasma levels. Thus, a continuous transmission risk from untraumatized genital epithelium exists in the majority of HIV-1-infected women at all stages of infection.
 ...
PMID:Distinct determinants of human immunodeficiency virus type 1 RNA and DNA loads in vaginal and cervical secretions. 959 6

The route of immunization may affect the type of immunity that is induced. The objectives of this investigation were to establish in the non-human primate if the internal iliac lymph nodes (LN) function as an inductive site of immunity from which mononuclear cells home to the rectal and cervico-vaginal mucosa. Rhesus macaques were immunized with simian immunodeficiency virus (SIV) core antigen p27 in the proximity of the iliac lymph nodes, and compared with the intramuscular (i.m.) (deltoid or gluteal), and axillary LN routes of immunization. The macaques were then challenged rectally or vaginally by a particulate SIVp27 antigen which was applied to the mucosal surface. The tracking dye PKH26 was injected near the immunizing LN or i.m. site and a week later the mucosal and lymphoid tissues were examined at autopsy. Preferential homing of PKH26-labeled cells from the internal iliac LN to the rectal and vaginal mucosa was demonstrated by flow cytometry after targeted iliac LN (TILN) but not after intramuscular (deltoid) or axillary LN immunization. Homing of the subsets of cells revealed that labeled CD4, CD8 and B cells, as well as monocytes were found in the rectum, colon, vagina or cervix. The results of this investigation shows that the route of immunization may affect regional mucosal immunity. Furthermore, the internal iliac LN may function as an inductive immunological site from which CD4, CD8 and B cells may home preferentially to the rectal, cervical and vaginal mucosa, as well as to the related regional but not the unrelated distal LN.
 ...
PMID:Homing of mononuclear cells from iliac lymph nodes to the genital and rectal mucosa in non-human primates. 980 75

The spread of sexually transmitted infections caused by herpes simplex virus type 2 (HSV-2) has continued unabated despite educational efforts generated in response to the human immunodeficiency virus (HIV) epidemic. Given the absence of effective vaccines, this indicates the need to develop prophylactic measures such as topical antiviral agents. Chemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor designated 3HP-beta-LG. This agent was shown to also have antiviral activity against HSV-2 and HSV-1 in vitro. Recent studies indicate that 3HP-beta-LG binds to HSV-1 virions, which, at least in part, involves the viral glycoprotein gE. Here we show that 3HP-beta-LG inhibits HSV-2 infection in the mouse model of genital HSV-2 infection. Simultaneous exposure to HSV-2 and 3HP-beta-LG caused a significant decrease in the proportion of infected animals (27% virus shedding, 5% lesion development and 0% fatality for 3HP-beta-LG as compared to 80% shedding, 60% lesion development and 53% fatality in mice treated with PBS). The proportion of animals with HSV-2 infection after treatment with beta-LG was similar to that in the PBS-treated group. Pretreatment with 3HP-beta-LG formulated in a gel, which prolongs the presence of the agent in the vagina, also significantly reduced the proportion of HSV-2-infected mice (5% virus shedding, 5% lesion development and 0% fatality for 3HP-beta-LG as compared to 70% shedding, 60% lesion development and 40% fatality in vehicle-treated mice). These differences were significant (P < or = 0.0005, 0.002 and 0.008 for shedding, lesion development and fatality, respectively). Virus titres in the minority of mice that developed infection were similar to those in untreated mice. HSV-2 infection was not inhibited by treatment of an ongoing infection, indicating that 3HP-beta-LG interferes with the initial infection. These data suggest that 3HP-beta-LG may be an efficacious agent for preventing vaginal transmission of genital herpesvirus infections.
 ...
PMID:3-Hydroxyphthaloyl beta-lactoglobulin. IV Antiviral activity in the mouse model of genital herpesvirus infection. 987 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>