Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A final step in retrovirus assembly, particle release from the cell, is modulated by a small motif in the Gag protein known as a late domain. Recently, human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (M-MuLV) were shown to require components of the cellular vacuolar protein sorting (VPS) machinery for efficient viral release. HIV-1 interacts with the VPS pathway via an association of HIV-1 Gag with TSG101, a component of the cellular complexes involved in VPS. Equine infectious anemia virus (EIAV) is unique among enveloped viruses studied to date because it utilizes a novel motif, YPDL in Gag, as a late domain. Our analysis of EIAV assembly demonstrates that EIAV Gag release is blocked by inhibition of the VPS pathway. However, in contrast to HIV-1, EIAV Gag release is insensitive to TSG101 depletion and EIAV particles do not contain significant levels of TSG101. Finally, we demonstrate that fusing EIAV Gag directly with another cellular component of the VPS machinery, VPS28, can restore efficient release of an EIAV Gag late-domain mutant. These results provide evidence that retroviruses can interact with the cellular VPS machinery in several different ways to accomplish particle release.
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PMID:Equine infectious anemia virus utilizes host vesicular protein sorting machinery during particle release. 1285 13

To assess the timing of symptomatic genital ulcer disease (GUD) relative to human immunodeficiency virus (HIV) seroconversion, we studied 248 case subjects who underwent HIV seroconversion and 496 HIV-negative control subjects, at 3 interview visits conducted at 10-month intervals: visit 1, before HIV acquisition; visit 2, after seroconversion; and visit 3, 10 months after detection of seroconversion. Odds ratios (ORs) and 95% confidence intervals (CIs), for HIV acquisition, were estimated by logistic regression. HIV load was measured by RNA-polymerase chain reaction, and herpes simplex virus type 2 (HSV-2) serologic testing used HerpeSelect EIA with Western blot confirmation. The OR of HSV-2 seropositivity associated with HIV acquisition was 1.7 (95% CI, 1.2-2.4). Prevalence of GUD was increased among case subjects, at visits 2 (OR, 3.2; 95% CI, 1.9-5.3) and 3 (OR, 2.1; 95% CI, 1.1-3.9). HIV load was increased in HSV-2-seropositive case subjects, compared with that in HSV-2-seronegative subjects, at 5 (P=.04) and 15 (P=.02) months after seroconversion. HIV acquisition is associated with HSV-2 seropositivity, and GUD is increased after seroconversion. HIV load is increased in HSV-2-positive subjects who seroconverted, suggesting a role for treatment of HSV-2 infection in HSV-2-seropositive, dually infected individuals.
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PMID:Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. 1462 74

Among animal lentiviruses, Feline immunodeficiency virus (FIV), Equine infectious anaemia virus (EIAV) and Small ruminant lentiviruses (SRLV) are important pathogens associated with a variety of clinical pictures including immunodeficiency, anaemia, arthritis, pneumonia. The detection of viral antibody response represents a practical diagnostic approach in all lentivirus infections since they remain detectable long life. Capsid antigen (CA) is the major viral core protein and specific antibodies against this antigen are usually first recognised in infected sheep, goat and horse, remaining detectable for long period. Transmembrane (TM) domain of envelope glycoprotein contains a well conserved motif known to form an immunodominant epitope in several lentiviruses. In this study a simple strategy was developed to express the entire CA and the TM epitope in a single fusion protein from equine, feline and small ruminant lentiviruses in prokaryotic system and evaluated the diagnostic utility of a purified preparation in an indirect ELISA for each of the three infections. Results demonstrate that, for FIV and SRLV infections, the combination of CA and TM fractions increases the sensitivity of diagnostic tests based only on CA. The corresponding CA/TM antigen from EIAV showed excellent agreement with Coggins test.
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PMID:Development of recombinant capsid antigen/transmembrane epitope fusion proteins for serological diagnosis of animal lentivirus infections. 1535 Jul 35

In 1994, zidovudine (ZDV) was demonstrated to substantially reduce perinatal transmission of the human immunodeficiency virus (HIV). Guidelines regarding the use of ZDV to reduce transmission and regarding counseling and voluntary testing of pregnant women were issued in 1994 and 1995, respectively. Surveillance methods were used to evaluate the implementation of these guidelines and to understand reasons for continued perinatal transmission of HIV. Population-based enhanced perinatal surveillance was used in seven states to collect information regarding mother-infant pairs in 1993, 1995, and 1996. Birth registries and HIV/Acquired immunodeficiency virus (AIDS) registries were matched to determine the number of HIV-infected women with diagnosis before delivery. Supplemental epidemiologic information was collected for 1,321 pairs. The estimated total number of HIV-infected women giving birth each year was derived from the Survey of Childbearing Women, an anonymous serologic survey of the prevalence of HIV infection among women giving birth. From 1993 through 1996, the proportion of HIV-infected women with diagnosis before delivery increased from 70% to 80%. The proportion of women with a diagnosis who received ZDV prenatally increased from 27% to 83% and intrapartum, 6% to 75%; for neonates, the increase was from 8% to 77%. Overall, 14% of women received no or only one prenatal care visit. A total of 36% of women who used illicit drugs during pregnancy had not had prenatal care. Of the children who received any ZDV, 8% were infected compared with 16% of those who received no ZDV. ZDV, used for treating pregnant HIV-infected women, has been rapidly adopted in clinical practice and has reduced the transmission of HIV. To achieve continued declines in perinatal transmission of HIV infection, continued progress is needed in the following areas: a) increases in the proportion of women who receive prenatal care and an HIV diagnosis; and b) implementation of rapid testing methods (when licensed rapid tests are available) or rapid turnaround of standard tests (expedited EIA tests).
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PMID:Successful implementation of perinatal HIV prevention guidelines. A multistate surveillance evaluation. 1558 Aug 1

A human immunodeficiency virus type 1 (HIV-1)/HIV-2 antibody screening assay, the Genetic Systems HIV-1/HIV-2 PLUS O EIA, was compared to several established screening or confirmatory tests using an acute HIV seroconversion panel. The HIV-1/HIV-2 PLUS O EIA showed an improved sensitivity over all tested antibody screening methods, and detected antibody in 7 of 19 specimens found to be negative by a first-generation EIA but positive for the presence of HIV RNA.
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PMID:Use of an acute seroconversion panel to evaluate a third-generation enzyme-linked immunoassay for detection of human immunodeficiency virus-specific antibodies relative to multiple other assays. 1667 22

The first diagnostic kits utilizing the enzyme-linked immunosorbent assay (ELISA) technique were developed in mid-eighties, and since then, this technique has become an increasingly important tool for screening multiple samples of blood or serum for presence of antibodies to various infectious pathogens, especially human immunodeficiency virus (HIV) in blood banks. However, most of the commercial diagnostic kits currently available in the market are too expensive, hence not easily affordable in most Diagnostic Laboratories. We designed an ELISA kit for diagnosis of HIV and compared it with some of the commercial kits. We used blood samples from the blood bank at the National Public Health Laboratory Services (NPHLS) in Nairobi and from patients referred to the Kenya Medical Research Institute (KEMRI) for HIV screening. Two commercial kits were used, Wellcozyme HIV Recombinant kit and Recombigen (env & gag) HIV-1 EIA kit. Out of 1350 samples tested by Recombigen (env & gag) HIV-1 EIA kit, 419 (31.0% ) were positive while 421 (31.2% ) samples were positive by Wellcozyme HIV Recombinant kit. Our ELISA kit detected a total of 431 positive samples out of 1350 (31.9% ), which was almost identical to the results from the other kits. Our kit was nearly identical in terms of sensitivity and specificity to the other two commercial kits used in this study. Thus our ELISA system, which is much cheaper than the commercial kits currently available in the market, offers a more affordable system for routine HIV tests.
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PMID:Evaluation of HIV ELISA diagnostic kit developed at the Institute of Primate Research, Nairobi, Kenya. 1729 54

Several factors including variability of human immunodeficiency virus (HIV), laboratory facilities, cost and competence of personnel handling the tests are some of the important factors that affect accuracy and reliability of HIV testing in most parts of Africa. Recently investigators in Africa have observed that antibody detection assays based on antigens derived from HIV-1 subtype B show moderate to significantly lower sensitivity for detection of infection by various non-B subtypes. In this study, we evaluated the reliability of two EIA and 12 rapid HIV-1/2 test kits that are commercially available in Nigeria using the Western immunoblotting technique as reference. A panel of 100 sera from Western blot confirmed symptomatic or asymptomatic HIV-1 infected persons and 90 seronegative patients from those referred for testing in our laboratory were used for this study. Each sample was tested with two HIV-1/2 EIA, and 12 HIV-1/2 rapid test kits commercially available at one time or the other for HIV-1/2 testing in Nigeria. Overall, the sensitivity of the two EIA kits were 100% and 91.0% with specificity of 96.7% and 91.1% respectively. The sensitivity of the rapid test kits ranged from 88% to 98.0% with specificity of 92.2% to 100%. Further analysis showed significant variation in the sensitivity and specificity of the same kit based on whether an individual had asymptomatic or symptomatic infection The results of this study highlight the problem of diagnosis of HIV infections in Africa. It shows that the sensitivity of most of the rapid assays shall not be adequate for detection of early infection. The implications of possible misdiagnosis on the various intervention strategies that rely predominantly on correct HIV status of an individual are enormous. Thus, there is an urgent need for review of the current HIV testing assays or algorithms in Nigeria and other parts of Africa.
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PMID:Reliability of testing and potential impact on HIV prevention in Nigeria. 1805 Jul 87

Equine infectious anemia virus (EIAV), uniquely among lentiviruses, does not encode a vif gene product. Other lentiviruses, including human immunodeficiency virus type 1 (HIV-1), use Vif to neutralize members of the APOBEC3 (A3) family of intrinsic immunity factors that would otherwise inhibit viral infectivity. This suggests either that equine cells infected by EIAV in vivo do not express active A3 proteins or that EIAV has developed a novel mechanism to avoid inhibition by equine A3 (eA3). Here, we demonstrate that horses encode six distinct A3 proteins, four of which contain a single copy of the cytidine deaminase (CDA) consensus active site and two of which contain two CDA motifs. This represents a level of complexity previously seen only in primates. Phylogenetic analysis of equine single-CDA A3 proteins revealed two proteins related to human A3A (hA3A), one related to hA3C, and one related to hA3H. Both equine double-CDA proteins are similar to hA3F and were named eA3F1 and eA3F2. Analysis of eA3F1 and eA3F2 expression in vivo shows that the mRNAs encoding these proteins are widely expressed, including in cells that are natural EIAV targets. Both eA3F1 and eA3F2 inhibit retrotransposon mobility, while eA3F1 is a potent inhibitor of a Vif-deficient HIV-1 mutant and induces extensive editing of HIV-1 reverse transcripts. However, both eA3F1 and eA3F2 are weak inhibitors of EIAV. Surprisingly, eA3F1 and eA3F2 were packaged into EIAV and HIV-1 virions as effectively as hA3G, although only the latter inhibited EIAV infectivity. Moreover, all three proteins bound both the HIV-1 and EIAV nucleocapsid protein specifically in vitro. It therefore appears that EIAV has evolved a novel mechanism to specifically neutralize the biological activities of the cognate eA3F1 and eA3F2 proteins at a step subsequent to virion incorporation.
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PMID:Equine infectious anemia virus resists the antiretroviral activity of equine APOBEC3 proteins through a packaging-independent mechanism. 1881 24

The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the Equine infectious anemia virus (EIAV), the Simian immunodeficiency virus (SIV), and the Adeno-associated virus type 2 (AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene.
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PMID:Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases. 1945 6

Prevention and regulation of equine infectious anemia virus (EIAV) disease transmission solely depend on identification, isolation, and elimination of infected animals because of lack of an effective vaccine. Embryo production via the somatic cell nuclear transfer (SCNT) technology uses oocytes collected mainly from untested animals, which creates a potential risk of EIAV transmission through infected embryos. The current review examines the risk of EIAV disease transmission through SCNT embryo production and transfer. Equine infectious anemia virus is a lentivirus from the family Retroviridae. Because of a lack of direct reports on this subject, relevant information gathered from close relatives of EIAV, such as human immunodeficiency virus (HIV), bovine immunodeficiency virus (BIV), feline immunodeficiency virus (FIV), and small ruminant lentiviruses (SRLVs), is summarized and used to predict the biological plausibility of EIAV disease transmission through transfers of the equine SCNT embryos. Based on published information regarding interaction of oocytes with lentiviruses and the sufficiency of oocyte and embryo washing procedures to prevent lentivirus transmission from in vitro-produced embryos of various species, we predicted the risk of EIAV transmission through SCNT embryo production and transfer to be very small or absent.
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PMID:Risk of equine infectious anemia virus disease transmission through in vitro embryo production using somatic cell nuclear transfer. 1948 52


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