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PubMed1995

Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95-116 as an HLA-DR2,w15-associated determinant.

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.

Adult↗
PubMed2000

Stallion epididymal fluid proteome: qualitative and quantitative characterization; secretion and dynamic changes of major proteins.

Proteins present in and secreted into the lumen of various regions of the stallion epididymis were characterized qualitatively and quantitatively by two-dimensional electrophoresis. Using this proteomic approach, 201 proteins were found in the lumen and 117 were found that were secreted by the epithelium in various parts of the organ. Eighteen proteins made up 92.6% of the total epididymal secretory activity, lactoferrin (41.2%) and clusterin (24.8%) being the most abundant. Procathepsin D, HE1/CTP (cholesterol transfer protein), GPX (glutathione peroxidase), beta-N-acetyl-hexosaminidase, and PGDS (prostaglandin D2 synthase) were the other major compounds secreted. The most abundant proteins found in the luminal fluid were albumin and the secreted proteins: lactoferrin, PGDS, GPX, HE1/CTP, and hexosaminidase. Three main secretory epididymal regions were identified from the protein pattern, i.e., regions E0-E2, E3-E5, and E6-E9. Region E0-E2 was characterized by the secretion of clusterin (53%), PGDS (44%), and GPX (6%). Region E3-E5 had the highest number of secreted proteins, the highest protein concentrations (60-80 mg/ml), and the highest spermatocrit value (85%). Lactoferrin (60% in E4), clusterin (29% in E3), hexosaminidase (10% in E3), and procathepsin D (6.9% in E4) were the most abundant proteins in this region. Region E6-E9, in which few region-specific secreted compounds were found, was characterized by a high quantity of lactoferrin in the luminal fluid (2-14 mg/ml). Comparison between the secretion of the major proteins and their concentrations in the lumen throughout the organ showed that the behavior of each protein is specific, in particular for the three isoforms of clusterin.

Amino Acid Sequence↗
PubMed1995

Flow cytometry reveals activated GP IIb-IIIa complexes on platelets from patients undergoing thrombolytic therapy after acute myocardial infarction.

We report the detection of activated GP IIb-IIIa complexes on platelets of patients undergoing thrombolytic therapy after acute myocardial infarction. Protocols were established for the monoclonal antibodies (mAbs): VH10, anti-P-selectin, a marker of platelet secretion; 9F9 and F26, two anti-RIBS (receptor-induced binding sites) mAbs specific for fibrinogen (Fg) bound to the GP IIb-IIIa receptor. Of ten patients studied: two were treated with streptokinase, four with APSAC (anisoylated plasminogen-streptokinase activator complex), and three with rt-PA. Platelets were tested on at least five occasions in the week following therapy. The percentage of platelets positive with 9F9 was often high, and reached a maximum within three days. By this time, plasma Fg levels, which fell during fibrinolysis, had begun to return to normal. Levels of activated platelets had fallen to baseline after 7 days. PAC-1, a mAb which binds directly to the activated GP IIb-IIIa complex, confirmed the results with 9F9, but F26 was a less sensitive probe. Binding of the anti-P-selectin mAb (VH10) was low, showing that little secretion had occurred. A concentration-dependent inhibition of 9F9 binding by RGDW peptide, a competitive inhibitor for Fg on GP IIb-IIIa, confirmed that Fg (or epitope-containing degradation products) were being located by the antibody. The activation of GP IIb-IIIa occurred despite the patients receiving aspirin and heparin. Thus platelets of some fibrinolytic patients have an increased tendency for surface activation within the first 72 h after treatment, a finding which would be compatible with an increased thrombotic tendency.

Adult↗
PubMed1993

Correlation between HIV provirus burden and in utero transmission.

OBJECTIVE: No predictive parameters of in utero or perinatal vertical transmission of HIV to newborns are known at present. Vertical transmission may be related to several biological parameters of maternal HIV infection: (1) immunological parameters (neutralizing antibodies); (2) the concentration of viral particles and/or infected cells; and (3) the selection of HIV subspecies of particular cellular tropism. The present study was designed to examine the relationship between cellular viral burden and transmission, and between maternal viral burden and CD4+ cell count and clinical status at delivery. METHOD: We investigated mother-to-infant HIV-1 transmission at delivery in a cohort of 51 pairs of mothers and newborns. Twelve infants were HIV-infected, as determined by successive polymerase chain reaction and culture determinations within the first 6 months of life, and nine of these were diagnosed as HIV-infected during the first week of life. We determined peripheral blood mononuclear cell proviral DNA burden using a quantitative polymerase chain reaction assay. Polymerase chain reaction was performed in the HIV-1 gag gene, using [32P]-end-labelled primers. External standard DNA samples were from the 85-14 F2 cell line, which contains a unique defective proviral DNA genome. RESULTS: There was a linear relationship between the logarithms of c.p.m. and the number of HIV-1 DNA copies. CONCLUSION: We have previously reported that the number of HIV provirus copies in maternal blood cells is related to transmission of the virus. Quantification of the HIV provirus by polymerase chain reaction may be used as a predictive parameter of vertical transmission if accompanied by an exhaustive clinical and biological follow-up during pregnancy.

Base Sequence↗
PubMed2002

Quorum sensing in Campylobacter jejuni: detection of a luxS encoded signalling molecule.

The expression of a wide variety of physiological functions in many bacterial species is modulated by quorum sensing, a population-dependent signalling mechanism that involves the production and detection of extracellular signalling molecules. The genome sequence of Campylobacter jejuni NCTC 11168 contains a gene encoding an orthologue of LuxS, which is required for autoinducer-2 (AI-2) production in other bacterial species, but does not contain genes predicted to encode any known acyl-homoserine lactone synthetase. This study demonstrates that C. jejuni produces functional AI-2 activity through the ability of cell-free extracts to specifically induce bioluminescence in Vibrio harveyi BB170, a reporter strain for quorum-sensing system 2. Production of this signalling compound was shown to be dependent upon the product of the C. jejuni luxS gene (Cj1198). While the luxS mutant showed comparable growth rate, resistance to oxidative stress and ability to invade Caco-2 cell monolayers to the parental strain, it exhibited decreased motility haloes in semisolid media, suggesting a role for quorum sensing in the regulation of motility.

Amino Acid Sequence↗
PubMed2004

Polymorphisms in the TNFA gene promoter region show evidence of strong linkage disequilibrium with HLA and are associated with delayed neutrophil engraftment in unrelated donor hematopoietic stem cell transplantation.

Sustained myeloid engraftment is an important determinant of outcome in hematopoietic stem cell transplantation (HSCT). Human tumor necrosis factor (TNF)-alpha is encoded by a gene, TNFA, located in the class III region of the major histocompatibility complex on chromosome 6, flanked by the human leukocyte antigen (HLA) class I and II regions. A number of polymorphisms in the promoter region of the TNFA gene have been associated with increased production of TNF-alphain vivo. Additionally, raised TNF-alpha levels have been reported to have a detrimental effect on the outcome in HSCT, in particular on early complications such as acute graft vs host disease, failure to engraft, and transplant-related mortality. There is evidence of linkage disequilibrium (LD) between TNFA promoter polymorphisms and extended HLA haplotypes. We have genotyped 73 cell lines and 189 donor/recipient pairs (undergoing HSCT) for their TNFA polymorphism, all of which had been well characterized with respect to their HLA genes. We found evidence of strong LD between HLA genes and TNFA; however, there was also evidence for recombination events having taken place, as we found that a number of transplant pairs who were matched for their HLA haplotypes were not matched for their TNFA alleles. We analyzed early outcomes in the transplant recipients and found a significant delay in engraftment in those pairs where both donor and recipients possessed an AG allele (associated with higher TNF-alpha levels). Our results suggest a functional effect of TNFA polymorphisms on myeloid engraftment in unrelated HSCT.

Adolescent↗
PubMed2001

Growth of chitinolytic dune soil beta-subclass Proteobacteria in response to invading fungal hyphae.

It has frequently been reported that chitinolytic soil bacteria, in particular biocontrol strains, can lyse living fungal hyphae, thereby releasing potential growth substrate. However, the conditions used in such assays (high bacterial density, rich media, fragmented hyphae) make it difficult to determine whether mycolytic activity is actually of importance for the growth and survival of chitinolytic bacteria in soils. An unidentified group of beta-subclass Proteobacteria (CbetaPs) was most dominant among the culturable nonfilamentous chitinolytic bacteria isolated from Dutch sand dune soils. Here we demonstrate that the CbetaPs grew at the expense of extending fungal mycelium of three dune soil fungi (Chaetomium globosum, Fusarium culmorum, and Mucor hiemalis) under nutrient-limiting, soil-like conditions. Aggregates of CbetaPs were also often found attached to fungal hyphae. The growth of a control group of dominant nonchitinolytic dune soil bacteria (beta- and gamma-subclass Proteobacteria) was not stimulated in the mycelial zone, indicating that growth-supporting materials were not independently released in appreciable amounts by the extending hyphae. Therefore, mycolytic activities of CbetaPs have apparently been involved in allowing them to grow after exposure to living hyphae. The chitinase inhibitor allosamidin did not, in the case of Mucor, or only partially, in the cases of Chaetomium and Fusarium, repress mycolytic growth of the CbetaPs, indicating that chitinase activity alone could not explain the extent of bacterial proliferation. Chitinolytic Stenotrophomonas-like and Cytophaga-like bacteria, isolated from the same dune soils, were only slightly stimulated by exposure to fungal hyphae.

Acetylglucosamine↗
PubMed2002

Bacteriocin-like activity of Butyrivibrio fibrisolvens JL5 and its effect on other ruminal bacteria and ammonia production.

When ruminal bacteria from a cow fed hay were serially diluted into an anaerobic medium that had only peptides and amino acids as energy sources, little growth or ammonia production was detected at dilutions greater than 10(-6). The 10(-8) and 10(-9) dilutions contained bacteria that fermented carbohydrates, and some of these bacteria inhibited Clostridium sticklandii SR, an obligate amino acid-fermenting bacterium. Phylogenetic analysis indicated that the most active isolate (JL5) was closely related to Butyrivibrio fibrisolvens B835. Strain JL5 inhibited B. fibrisolvens 49 and a variety of other gram-positive organisms, but it had little effect on most gram-negative ruminal bacteria. Strain JL5 did not produce a bacteriocin-like inhibitory substance (BLIS) until it reached the late log or stationary phase. The JL5 BLIS did not cause the lysis of B. fibrisolvens 49, but the intracellular potassium level, the ATP level, the electrical potential, and the viability decreased rapidly. The JL5 BLIS also caused marked decreases in the viability and cellular potassium level of C. sticklandii SR. The membrane potential and intracellular ATP level also declined. The BLIS was degraded very slowly by pronase E, but it could be precipitated with 60% ammonium sulfate and dialyzed (3,500-Da cutoff). The BLIS could be separated from other peptides by polyacrylamide gel electrophoresis, and C. sticklandii SR overlays indicated that the molecular size of this compound was approximately 3,600 Da. Based on these results, it appeared that the JL5 BLIS was a pore-forming peptide. Because carbohydrate-fermenting ruminal bacteria could inhibit the growth of obligate amino acid-fermenting bacteria, BLIS may play a role in regulating ammonia production in vivo.

Amino Acids↗
PubMed2003

Microbial community composition affects soil fungistasis.

Most soils inhibit fungal germination and growth to a certain extent, a phenomenon known as soil fungistasis. Previous observations have implicated microorganisms as the causal agents of fungistasis, with their action mediated either by available carbon limitation (nutrient deprivation hypothesis) or production of antifungal compounds (antibiosis hypothesis). To obtain evidence for either of these hypotheses, we measured soil respiration and microbial numbers (as indicators of nutrient stress) and bacterial community composition (as an indicator of potential differences in the composition of antifungal components) during the development of fungistasis. This was done for two fungistatic dune soils in which fungistasis was initially fully or partly relieved by partial sterilization treatment or nutrient addition. Fungistasis development was measured as restriction of the ability of the fungi Chaetomium globosum, Fusarium culmorum, Fusarium oxysporum, and Trichoderma harzianum to colonize soils. Fungistasis did not always reappear after soil treatments despite intense competition for carbon, suggesting that microbial community composition is important in the development of fungistasis. Both microbial community analysis and in vitro antagonism tests indicated that the presence of pseudomonads might be essential for the development of fungistasis. Overall, the results lend support to the antibiosis hypothesis.

Antibiosis↗
PubMed2003

Microbial quality and direct PCR identification of lactic acid bacteria and nonpathogenic Staphylococci from artisanal low-acid sausages.

Detection of six species of lactic acid bacteria and six species of gram-positive catalase-positive cocci from low-acid fermented sausages (fuets and chorizos) was assessed by species-specific PCR. Without enrichment, Lactobacillus sakei and Lactobacillus curvatus were detected in 11.8% of the samples, and Lactobacillus plantarum and Staphylococcus xylosus were detected in 17.6%. Enriched samples allowed the detection of L. sakei and S. xylosus in all of the samples (100%) and of Enterococcus faecium in 11.8% of the sausages. The percentages of L. curvatus, L. plantarum, Staphylococcus carnosus, and Staphylococcus epidermidis varied depending on the sausage type. L. curvatus was detected in 80% of fuets and in 57% of chorizos. L. plantarum was found in 50% of fuets and 100% of chorizos. S. epidermidis was detected in only 11.8% of fuets, and S. carnosus was detected in only 5.9% of chorizos. Lactococcus lactis, Staphylococcus warneri, and Staphylococcus simulans were not detected in any sausage type. From a microbiological point of view, 70.6% of the samples could be considered of high quality, as they had low counts of Enterobacteriaceae and did not contain any of the food-borne pathogens assayed.

Base Sequence↗
PubMed2004

N2 fixation by unicellular bacterioplankton from the Atlantic and Pacific oceans: phylogeny and in situ rates.

N2-fixing proteobacteria (alpha and gamma) and unicellular cyanobacteria are common in both the tropical North Atlantic and Pacific oceans. In near-surface waters proteobacterial nifH transcripts were present during both night and day while unicellular cyanobacterial nifH transcripts were present during the nighttime only, suggesting separation of N2 fixation and photosynthesis by unicellular cyanobacteria. Phylogenetic relationships among unicellular cyanobacteria from both oceans were determined after sequencing of a conserved region of 16S ribosomal DNA (rDNA) of cyanobacteria, and results showed that they clustered together, regardless of the ocean of origin. However, sequencing of nifH transcripts of unicellular cyanobacteria from both oceans showed that they clustered separately. This suggests that unicellular cyanobacteria from the tropical North Atlantic and subtropical North Pacific share a common ancestry (16S rDNA) and that potential unicellular N2 fixers have diverged (nifH). N2 fixation rates for unicellular bacterioplankton (including small cyanobacteria) from both oceans were determined in situ according to the acetylene reduction and 15N2 protocols. The results showed that rates of fixation by bacterioplankton can be almost as high as those of fixation by the colonial N2-fixing marine cyanobacteria Trichodesmium spp. in the tropical North Atlantic but that rates are much lower in the subtropical North Pacific.

Animals↗
PubMed2005

Source bioaerosol concentration and rRNA gene-based identification of microorganisms aerosolized at a flood irrigation wastewater reuse site.

Reuse of partially treated domestic wastewater for agricultural irrigation is a growing practice in arid regions throughout the world. A field sampling campaign to determine bioaerosol concentration, culturability, and identity at various wind speeds was conducted at a flooded wastewater irrigation site in Mexicali, Baja California, Mexico. Direct fluorescent microscopy measurements for total microorganisms, culture-based assays for heterotrophs and gram-negative enteric bacteria, and small-subunit rRNA gene-based cloning were used for microbial characterizations of aerosols and effluent wastewater samples. Bioaerosol results were divided into two wind speed regimens: (i) below 1.9 m/s, average speed 0.5 m/s, and (ii) above 1.9 m/s, average speed 4.5 m/s. Average air-borne concentration of total microorganisms, culturable heterotrophs, and gram-negative enteric bacteria were, respectively, 1.1, 4.2, and 6.2 orders of magnitude greater during the high-wind-speed regimen. Small-subunit rRNA gene clone libraries processed from samples from air and the irrigation effluent wastewater during a high-wind sampling event indicate that the majority of air clone sequences were more than 98% similar to clone sequences retrieved from the effluent wastewater sample. Overall results indicate that wind is a potential aerosolization mechanism of viable wastewater microorganisms at flood irrigation sites.

Aerosols↗
PubMed2006

In vivo random mutagenesis of Bacillus subtilis by use of TnYLB-1, a mariner-based transposon.

This report describes the construction and characterization of a mariner-based transposon system designed to be used in Bacillus subtilis, but potentially applicable to other gram-positive bacteria. Two pUC19-derived plasmids were created that contain the mariner-Himar1 transposase gene, modified for expression in B. subtilis, under the control of either sigmaA- or sigmaB-dependent promoters. Both plasmids also contain a transposable element (TnYLB-1) consisting of a Kan r cassette bracketed by the Himar1-recognized inverse terminal repeats, as well as the temperature-sensitive replicon and Erm r gene of pE194ts. TnYLB-1 transposes into the B. subtilis chromosome with high frequency (10(-2)) from either plasmid. Southern hybridization analyses of 15 transposants and sequence analyses of the insertion sites of 10 of these are consistent with random transposition, requiring only a "TA" dinucleotide as the essential target in the recipient DNA. Two hundred transposants screened for sporulation proficiency and auxotrophy yielded five Spo- clones, three with insertions in known sporulation genes (kinA, spoVT, and yqfD) and two in genes (ybaN and yubB) with unknown functions. Two auxotrophic mutants were identified among the 200 transposants, one with an insertion in lysA and another in a gene (yjzB) whose function is unknown.

Bacillus subtilis↗
PubMed1995

Cytokine mRNA profiles in mononuclear cells in acute aseptic meningoencephalitis.

Cytokines are important modulators of inflammation and immune responses. Using in situ hybridization with radiolabelled cDNA oligonucleotide probes, we studied the expression of mRNA encoding the cytokines gamma interferon (IFN-gamma), interleukin 4 (IL-4), IL-6, IL-10, transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), lymphotoxin, and perforin in mononuclear cells (MNC) from blood and cerebrospinal fluid (CSF) of patients with acute aseptic meningoencephalitis (AM) and from blood of healthy controls. Patients in the acute phase of AM had elevated numbers of IFN-gamma mRNA-expressing cells in the blood compared with that of controls and higher numbers of IFN-gamma mRNA-expressing cells in their CSF compared with that of convalescent-phase patients, which is in accordance with the antiviral effects of this cytokine. Upregulation of IL-4, IL-6, and IL-10 was found in convalescent-phase patients, which is consistent with the longstanding B-cell response found in AM. TGF-beta and perforin were upregulated in both stages of AM, while the numbers of blood and CSF MNC expressing cytokine mRNA of the TNF family (TNF-alpha and lymphotoxin) did not differ between patients with AM and controls. An even higher elevation in CSF was noticed for MNC expressing most of the cytokines, particularly IL-4 and TGF-beta, reflecting the autonomy of the immune response in the CSF. The definition of cytokine profiles in AM, a self-limiting and benign disease, provides a foundation for future comparisons with other infectious and inflammatory nervous system diseases.

Acute Disease↗
PubMed2001

Cell density modulates acid adaptation in Streptococcus mutans: implications for survival in biofilms.

Streptococcus mutans normally colonizes dental biofilms and is regularly exposed to continual cycles of acidic pH during ingestion of fermentable dietary carbohydrates. The ability of S. mutans to survive at low pH is an important virulence factor in the pathogenesis of dental caries. Despite a few studies of the acid adaptation mechanism of this organism, little work has focused on the acid tolerance of S. mutans growing in high-cell-density biofilms. It is unknown whether biofilm growth mode or high cell density affects acid adaptation by S. mutans. This study was initiated to examine the acid tolerance response (ATR) of S. mutans biofilm cells and to determine the effect of cell density on the induction of acid adaptation. S. mutans BM71 cells were first grown in broth cultures to examine acid adaptation associated with growth phase, cell density, carbon starvation, and induction by culture filtrates. The cells were also grown in a chemostat-based biofilm fermentor for biofilm formation. Adaptation of biofilm cells to low pH was established in the chemostat by the acid generated from excess glucose metabolism, followed by a pH 3.5 acid shock for 3 h. Both biofilm and planktonic cells were removed to assay percentages of survival. The results showed that S. mutans BM71 exhibited a log-phase ATR induced by low pH and a stationary-phase acid resistance induced by carbon starvation. Cell density was found to modulate acid adaptation in S. mutans log-phase cells, since pre-adapted cells at a higher cell density or from a dense biofilm displayed significantly higher resistance to the killing pH than the cells at a lower cell density. The log-phase ATR could also be induced by a neutralized culture filtrate collected from a low-pH culture, suggesting that the culture filtrate contained an extracellular induction component(s) involved in acid adaptation in S. mutans. Heat or proteinase treatment abolished the induction by the culture filtrate. The results also showed that mutants defective in the comC, -D, or -E genes, which encode a quorum sensing system essential for cell density-dependent induction of genetic competence, had a diminished log-phase ATR. Addition of synthetic competence stimulating peptide (CSP) to the comC mutant restored the ATR. This study demonstrated that cell density and biofilm growth mode modulated acid adaptation in S. mutans, suggesting that optimal development of acid adaptation in this organism involves both low pH induction and cell-cell communication.

Amino Acid Sequence↗
PubMed1994

Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA.

Infection of injury results in several systemic and central reactions termed the acute phase response (APR). Substantial evidence suggests that cytokines induced by microbes initiate the APR. We compared the APR induced in rabbits by a model bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were also determined. Rabbits were injected intravenously or intracerebroventricularly with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood samples were taken at the time of injection and at 3, 6, and 24 h after injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the intravenous route increased fibrinogen, whereas only intravenously injected poly I:C induced antiviral activity. Intracerebroventricular injections of LPS and poly I:C also elicited dose-dependent febrile responses but did not change the hematologic APR significantly except for fibrinogen. The primary distinctions between LPS and poly I:C with respect to cytokine induction in the RAW 264.7 macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly I:C.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗
PubMed2001

Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins.

Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8 infection, including clinical outcome and host immune responses that may be important in preventing disease related to HHV-8, has not been elucidated. The present study characterized the clinical, immunologic, and virologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seronegative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild, nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and lymphadenopathy. There were no alterations in numbers of CD4(+) or CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-gamma) production to mitogen or nominal antigen. CD8(+) cytotoxic T-lymphocyte precursor (CTLp) and IFN-gamma reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in association with increases in serum antibody titers and appearance of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may control initial HHV-8 infection and prevent development of disease.

Adult↗