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

HIV infection of chimpanzees results in a chronic viremia unaccompanied by the ultimately fatal immunodeficiency that marks HIV infection in man. We show here that expression of HIV envelope proteins allows syncytium formation between cells expressing human but not chimpanzee or macaque CD4. We find that the CD4 sequences regulating cell fusion lie outside the recognized virus binding site; in the simplest exchange, chimpanzee CD4 bearing human residue 87 supports syncytium formation, while human CD4 bearing chimpanzee residue 87 does not. Neither the equilibrium nor the forward rate constants for HIV-CD4 association are affected by substitution at position 87. Infection of human cells expressing chimpanzee CD4 is insensitive to lysosomotropic agents, suggesting that viral penetration under these circumstances does not require endocytosis. The benign course of HIV infection in chimpanzees may reflect the failure of the host to support direct cell to cell transmission of the virus.
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PMID:A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site. 210 24

We tried to assess the long-term safety and potential efficacy of passive immunization in AIDS-related-complex (ARC) and AIDS patients. We also wanted to establish whether hyperimmune plasma from healthy human immunodeficiency virus 1 (HIV-1)-infected individuals clears the cell-free virus from circulation. Using the polymerase chain reaction (PCR), we were able to provide conclusive evidence that hyperimmune plasma is effective and maintains long-term neutralization of viremia. Using the cell test, we found that in most patients the total antibody level was maintained; in one of the ARC patients, it actually increased 8-fold and has remained at that level for nearly 2 years. The CD4+ cell count decreased in the AIDS patients but was stable in the ARC patient. Clinically, there was an initial improvement in all patients, but five of six of the advanced/terminal AIDS patients had died by month 17. Our studies suggest that passive immunization may be safe in ARC and AIDS patients. It reduces HIV-1 viremia to levels undetectable even by PCR. To advanced/terminal patients, the benefit is of limited duration, while to ARC patients it may be long-term. Therefore, passive immunization should start early in the disease.
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PMID:Polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with AIDS and AIDS-related complex. 214 79

Sera from 353 cats with naturally occurring feline leukemia virus (FeLV) infection were collected in Boston, Los Angeles, New York City, and Seattle between 1968 and 1988. These sera were retrospectively assayed by enzyme-linked immunosorbent assay for antibodies to feline immunodeficiency virus (FIV). Fifty-one (14.4%) of the FeLV-positive sera had antibodies to FIV, indicating dual oncovirus and lentivirus infections. FIV infections were confirmed by Western blot analysis, antibodies against the 15 and 27 kDa proteins being used as definitive markers. FIV infection was diagnosed in one cat sampled in 1968 and in eight other cats sampled before 1975 in New York City. Illnesses exhibited by coinfected cats were similar to those of cats infected with FeLV only. Two unrelated cats with multicentric fibrosarcomas were found to be simultaneously infected with FIV, FeLV, and feline sarcoma virus. FIV was less contagious than FeLV in 73 cats residing in an exposure household between 1977 and 1980 as determined by evaluation of sera collected sequentially. In this household, 15 resident cats became FeLV infected whereas no cats contracted FIV infection. Comparison of serologic results from 53 cats with leukemia/lymphoma and matched controls confirmed a strong correlation between FeLV viremia and leukemia/lymphoma. A significant correlation between FIV infection and lymphoproliferative malignancies was also found independent of FeLV infection.
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PMID:Feline immunodeficiency virus and feline leukemia virus infections and their relationships to lymphoid malignancies in cats: a retrospective study (1968-1988). 215 93

An infectious, virulence-attenuated molecular clone of simian immunodeficiency virus (SIV), SIVMAC-1A11, was derived from an SIV isolate that causes fatal immunodeficiency in rhesus macaques. When inoculated intravenously in rhesus macaques, SIVMAC-1A11 induced transient viremia (1 to 6 weeks) without clinical disease and a persistent humoral antibody response. The antibodies were directed mainly against the viral envelope glycoproteins, as determined by immunoblots and virus neutralization. The potential of this virulence-attenuated virus to protect against intravenous challenge with a pathogenic SIVMAC strain was assessed. Five rhesus macaques were each given two intravenous inoculations with SIVMAC-1A11 7 months apart. Three of the five immunized monkeys and four naive control animals were then challenged with 100 to 1,000 100% animal infectious doses of pathogenic SIVMAC. All seven animals became persistently viremic following the challenge. Four of four unimmunized animals developed severe clinical signs of simian acquired immunodeficiency syndrome by 38 to 227 days after challenge and were euthanatized 91 to 260 days postchallenge. However, no signs of illness were seen in immunized monkeys until 267 to 304 days postchallenge, when two of three immunized animals developed mild thrombocytopenia and lymphopenia; one of these animals died with clinical signs of simian immunodeficiency disease at 445 days after challenge. The two SIVMAC-1A11-immunized monkeys that were not challenged were healthy and antibody positive 22 months after the initial immunization. Thus, although live SIVMAC-1A11 was immunogenic and did not induce any disease, it failed to protect rhesus macaques against infection with a moderately high dose of pathogenic virus. However, immunization prevented severe, early disease and prolonged the lives of monkeys subsequently infected with pathogenic SIV.
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PMID:Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. 216 91

The pandemic of the acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus type 1 (HIV-1), requires rapid development of effective therapy and prevention. Analysis of candidate anti-HIV-1 drugs in animals is problematic since no ideal animal model for HIV-1 infection and disease exists. For many reasons, including small size, availability of inbred strains, immunological reagents, and lymphokines, murine systems have been used for in vivo analysis of antiretroviral agents. Here we review currently available murine models involving HIV-1 in transgenic mice and in chimeric mice reconstituted with human cells, as well as murine systems using retroviruses of the subfamily Oncovirinae rather than Lentivirinae. We report our results on various antiretroviral treatment strategies, including chemoprophylaxis after acute retroviral exposure, therapy of chronic viremia, quantitative analysis of combination therapy, and therapy during pregnancy and in the neonatal period aimed at preventing viremia in the offspring. Due to our highly effective postexposure treatment protocols with 3'-azido-3'-deoxythymidine (zidovudine) combined with recombinant human interferon-alpha A/D, retrovirus-inoculated mice developed immunity to the virus to which they were exposed, which will allow us to determine the nature of protective antiretroviral immunity in inbred mice.
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PMID:Murine models for evaluating antiretroviral therapy. 216 58

A central anomaly in the pathogenesis of AIDS is that few actively infected CD4+ cells (1 in 10(4)-10(5) have been detected in the peripheral blood, even though dramatic depletion (often greater than 90%) of CD4+ cells is the hallmark of disease progression. A sensitive, 35S-based human immunodeficiency virus (HIV) RNA in situ hybridization technique was coupled with a new detection method, confocal laser scanning microscopy, to examine transcriptionally active HIV-infected cells from individuals at different disease stages. In 35 symptomatic HIV-infected individuals (AIDS and AIDS related complex), an average of 1 in 350 mononuclear cells produced HIV RNA. In contrast, in an asymptomatic group of 30 individuals, an average of 1 in 2000 mononuclear cells produced HIV RNA. These data, obtained using this improved detection method, suggest there are more HIV RNA-producing cells in HIV-infected individuals than previously reported. In addition, increased numbers of HIV transcribing cells were found to correlate with declining clinical condition as assessed by Karnofsky performance score. These data suggest that viremia per se may account for the pathologic consequences in HIV infection.
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PMID:Confocal microscopic detection of human immunodeficiency virus RNA-producing cells. 223 Feb 69

A single application of trypan blue 3 to 24 hours before or simultaneous with inoculation of the Rauscher leukemia virus (RLV) resulted in enhancement of leukemogenesis with an especially high viremia. Repeated administration of trypan blue after RLV infection resulted in reduced spleen weight. Viremia, however, was also increased compared with controls (no application of trypan blue), but in a lower rate than in mice treated with the virus plus trypan blue. Since trypan blue is known as an inhibitor of the functions of macrophages the results point at an important role of this cell type in preventing infection with this oncogenic retrovirus. In this regard there are differences in the role of macrophages in human immunodeficiency virus (HIV) infections.
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PMID:[The influence of macrophages on the leukemogenic activity of Rauscher murine leukemia virus]. 239 4

The inhibition of viremia and p24 core antigenemia in patients infected with human immunodeficiency virus (HIV) was evaluated in separate multicenter, double-blind, placebo-controlled trials of zidovudine and ribavirin. Of 29 patients (14 with AIDS and 15 with AIDS-related complex [ARC]) enrolled in the zidovudine study, 16 received 250 mg of zidovudine every 4 h and 13 received placebo. No difference in HIV isolation from peripheral blood was observed at 20 w in treated versus placebo groups (79% vs. 82%). In patients tolerating zidovudine, mean p24 antigen levels dropped to 8.2% +/- 8.1% of their baseline values, whereas in placebo recipients mean p24 antigen levels declined to 61.3% +/- 40.8% of their baseline values (P less than .005). In the ribavirin study, patients with ARC treated with either 800 mg or 600 mg ribavirin daily or with placebo showed no consistent reduction in p24 antigenemia or decrease in HIV isolation. These data indicate that decline in p24 antigenemia can be a useful virologic marker in evaluation of new antiretroviral drugs.
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PMID:The antiviral effect of zidovudine and ribavirin in clinical trials and the use of p24 antigen levels as a virologic marker. 249 73

Attempts to isolate human immunodeficiency virus type 1 (HIV-1) were carried out on cerebrospinal fluid (CSF) and blood plasma samples from 111 HIV-1 infected subjects in various stages of infection. HIV-1 was recovered at a low rate from CSF of persons with normal immunological parameters but frequently from patients with abnormal values, in all stages of immune system involvement. Isolation from plasma was positive in the majority of the patients, in all stages of infection, with a frequency that was related to the degree of immunodeficiency. HIV-1 could be recovered from the CSF of most patients (74%) with viremia when 85 paired specimens of 58 patients were analyzed. By contrast, HIV-1 was isolated from CSF, but not from plasma, in one case only. HIV-1 p24 antigen measured by an enzyme-linked immunosorbent assay (ELISA) was detectable in only four CSF samples compared with 15 serum samples in paired specimens. These findings indicate that most patients with HIV-1 infection have circulating cell-free infectious virus in the blood and simultaneously demonstrable HIV-1 in the CSF. Replication of HIV-1 exclusively in the central nervous system (CNS) appears to be a rare event.
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PMID:Relationship between the occurrence of virus in plasma and cerebrospinal fluid of HIV-1 infected individuals. 249 61

To determine which markers of human immunodeficiency virus type 1 (HIV) replication correlate most closely with progressive disease, we compared the following: (1) the frequency of isolation of HIV from peripheral-blood mononuclear cells (PBMC), (2) the frequency of isolation of the virus from cell-free plasma (plasma viremia), (3) the presence and titer of p24 antigen in plasma, and (4) the presence and titer of antibody to p24 antigen. We studied 213 persons who were positive for HIV antibody and 71 who were negative. HIV was isolated from PBMC from 207 of the 213 antibody-positive patients (97 percent), regardless of the clinical stage of the infection. Plasma viremia, in contrast, was correlated with the clinical stage of the infection. It was detected in 11 of 48 patients (23 percent) with asymptomatic infection, 32 of 71 (45 percent) in Class IVa of the Centers for Disease Control (those with AIDS-related complex), and 75 of 92 (82 percent) in Class IVc (those with AIDS) (P less than 0.01). Plasma HIV titers ranged from 10(0) to 10(4.3) and rose from a mean of 10(1.4) in asymptomatic patients to 10(2.5) in those with AIDS (P less than 0.02). Only 45 percent of patients with plasma viremia had HIV p24 antigen in either serum or plasma, and no correlation was found between the amount of p24 antigen in plasma and the plasma HIV titers. Follow-up tests indicated that plasma viremia was associated with a more marked decline in the CD4-lymphocyte cell count and the development of symptomatic disease (P = 0.034). We conclude that plasma viremia is a more sensitive virologic marker of the clinical stage of HIV infection and viral replication than the presence of p24 antigen or antibody in plasma. Not only whole blood but cell-free plasma from HIV-infected patients should be considered potentially infectious.
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PMID:Plasma viremia in human immunodeficiency virus infection. 258 69


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