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S L Valle

Publications and source records attributed to S L Valle.

At least 19 recordsLinked to original sources

B-cell epitopes in HIV-1 Tat and Rev proteins colocalize with T-cell epitopes and with functional domains.

We describe the characterization of the B-cell epitopes of HIV-1 regulatory proteins Tat and Rev. The prevalence of antibodies to these proteins among human immunodeficiency virus (HIV)-1-infected individuals was examined by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The Tat and Rev antibody-positive sera were selected for epitope mapping performed with partially overlapping synthetic peptides bound to polyethylene pins. Eighteen and twelve percent of HIV-infected individuals had antibodies against Tat or Rev, respectively. In Tat, four epitopic regions were identified, situated within amino acids 6-10 (PRLEP), 21-37 (ACTNCYCKKCCFHCQVC), 39-58 (ITKALGISYGRKKRRQRRRA) and 74-82 (TSQSRGDPT). The most frequently recognized epitopic regions were located in the middle of the protein. In Rev, the two most frequently recognized epitopic regions were near the amino terminus of the protein within amino acids 12-20 (LIRTVRLIK) and 38-49 (RRNRRRRWRERQ). A third epitope was mapped around amino acids 55-62 (ISERILGT) and a fourth around amino acids 78-83 (LERLTU). To analyze the specificity of Tat and Rev epitopes, soluble synthetic peptides representing the identified epitopes were used in an ELISA assay, and the recognition of most epitopes was shown to be specific for HIV-1-infected individuals. In addition, many of the Tat and Rev epitopes were shown to overlap with regions having functional activity or with regions previously identified as T-cell epitopes.

Amino Acid Sequence↗

Cognitive performance in HIV-1 infection: relationship to severity of disease and brain atrophy.

We examined cognitive performance in 72 HIV-1 infected patients and 34 controls. None of the patients had opportunistic infections or unusual neoplasms of the central nervous system (CNS). Factors other than HIV-1 known to cause cognitive decline were excluded from both groups. Cognitive functioning analysed with special emphasis on the severity of HIV infection was related to neuroradiological and immunological findings. In patients with AIDS-related complex (CDC IVa) or AIDS (CDC IVc,d), a deterioration of memory as well as cognitive speed and flexibility was detected. Furthermore, memory deficits were associated with central cerebral and infratentorial atrophy in those patients, while no association was found between cognitive deficits and immunological abnormalities. Patients at CDC stages II or III showed slight association between altered cognitive speed and flexibility and elevated leukocyte count, suggesting a subclinical CNS disease already at early stages of HIV infection.

AIDS Dementia Complex↗

Helper T-cell recognition of HIV-1 Tat synthetic peptides.

The regulatory proteins coded by the human immunodeficiency virus, (HIV)-1 genome are expressed by the infected cells before the initiation of the synthesis of structural proteins and thus immune response directed against these proteins could destroy infected cells before the release of infectious virions. The evaluation of T-lymphocyte responses toward Tat, one of the main HIV-1 regulatory proteins, is therefore of interest. We selected a group of HIV-infected patients with retained response to the recall antigen purified protein derivative and tested their CD4+ helper T-cell response toward recombinant Tat and toward 12 soluble synthetic partially overlapping 15-16-mer Tat peptides in a proliferation assay. Three peptides (amino acids 17-32, 33-48, and 65-80) were significantly recognized by the helper T-cells from infected individuals but not by the nine HIV-1-negative control persons. Nine of the 14 patients (64%) responded to at least one of these Tat peptides. Of the identified immunodominant peptides containing T-cell epitopes, one (aa 65-80) was recognized in association with human leukocyte antigens DR-2 allele, while the others appeared to be promiscuous and were equally recognized in association with several DR molecules. The identified immunogenic peptides were analyzed for the predicted presence of T-cell antigenic sites by several algorithms and positive correlation was detected for each peptide. Our results thus indicate that Tat protein can induce a cell-mediated immune response and identify three peptides containing T-cell epitopes that may be of importance in vaccine development.

Alleles↗

Radiological study of the brain at various stages of human immunodeficiency virus infection: early development of brain atrophy.

One hundred and one persons infected with human immunodeficiency virus (HIV-1), in whom other central nervous system infections or diseases were excluded, underwent brain CT and/or MRI at various stages of HIV-1 infection: 29 were asymptomatic (ASX), 35 had lymphadenopathy syndrome (LAS), 17 had AIDS-related complex (ARC), and 20 had AIDS. A control group of 32 HIV-1-seronegative healthy persons underwent brain MRI. The most common finding was brain atrophy, found in 9% of controls, and 31% of ASX cases, 29% of LAS, 59% of ARC and 70% of AIDS. Even the difference between the ASX or LAS groups and controls was significant. The changes were bilateral and symmetrical, and they were more severe at later stages of infection. Infratentorial atrophy was seen in the early stages; supratentorial atrophy became more pronounced at ARC, and generalized atrophy was typical of AIDS. Non-specific small hyperintense foci were found on MRI in 13% of controls and 6-15% of the infected groups. Larger, diffuse, bilateral white matter infiltrates were detected in 4 demented patients with AIDS. Four patients with AIDS and 1 with LAS had focal hyperintense lesions in the internal capsules, lentiform nuclei or thalamus, often bilateral on MRI. One patient with AIDS, examined with CT only, had low density in the lentiform nucleus. Loss of brain parenchyma can occur at an early stage of HIV-1 infection, and the atrophic process becomes more intense at later stages (ARC and AIDS). Parenchymal infiltration, seen as hyperintense areas on MRI, is most often associated with severe clinical symptoms, in the later stages of the disease.

Acquired Immunodeficiency Syndrome↗

Serological responses to mycoplasmas in HIV-infected and non-infected individuals.

OBJECTIVE: To assess the frequency of mycoplasma infections in HIV-antibody-positive and -negative individuals by studying the serological responses against mycoplasmas, especially Mycoplasma fermentans and M. pirum. DESIGN: An enzyme-linked immunosorbent assay (ELISA) was used to measure immunoglobulin G (IgG) class antibody concentrations against six mycoplasma species in sera of HIV-positive and HIV-negative individuals. METHODS: Serum samples were obtained from 30 HIV-positive individuals (10 asymptomatics, 10 with lymphadenopathy syndrome and 10 with AIDS), 10 HIV-negative partners of HIV-positive individuals and 40 HIV-negative blood donors. Antibodies to M. fermentans strains incognitus and PG18, M. pirum, M. genitalium, M. pneumoniae and M. hominis were assessed by immunoblot or ELISA. Absorbance values were taken as a semiquantitative measurement for antibody concentration and an arbitrary cut-off value (0.8) was set to establish seroprevalence. RESULTS: There was no significant difference in the mean IgG concentrations of any of the six mycoplasmas between HIV-positive and HIV-negative groups. Antibody concentrations were also similar in different clinical phases of HIV infection. Antibody concentrations to different mycoplasma strains were compared with each other to reveal eventual cross-reactions caused by shared antigens; the strongest correlation (r = 0.836) was found between M. fermentans strains incognitus and M. pirum antibody concentrations. The correlation between M. fermentans strains incognitus and PG18 was also significant but weaker (r = 0.522). No shared antigens between M. fermentans strain incognitus and M. pirum were demonstrated by immunoblot. CONCLUSIONS: Antibodies against M. fermentans type strain PG18, strain incognitus and against M. pirum are detected infrequently and their presence does not correlate with HIV infection per se or with the clinical stage of HIV infection.

Antibodies, Bacterial↗

EEG in early HIV-1 infection is characterized by anterior dysrhythmicity of low maximal amplitude.

We analyzed the EEGs of 67 HIV-1-infected patients at various stages of the disease and of 35 HIV-1-seronegative controls. The most common EEG abnormality in HIV-1 infection was an increased amount of generalized episodic or persistent, predominantly anterior slow activity, associated with a low level of maximal amplitude. When compared to the controls, a lower maximal amplitude of dominant background activity (p less than 0.001), and more marked generalized (p less than 0.01) and anterior (p less than 0.001) disturbances were already seen in early stages of HIV-1 infection. EEG abnormalities were more severe in patients with advanced HIV-1 infection than in those at early infection (p less than 0.001 to p less than 0.05). The presence of a more marked, posteriorly (p less than 0.01) accentuated, generalized slow activity (p = 0.02) was found more often in patients with T-helper cell counts lower than 0.4 x 10(9) (p = 0.05) than in those with higher numbers of T-helper cells. No clear associations were found between the severity of EEG abnormalities and the duration of HIV-1 infection. Our results suggest that EEG is a sensitive method in detecting subclinical functional cerebral disturbances caused by HIV-1.

AIDS Dementia Complex↗

HIV antibodies in whole saliva detected by ELISA and western blot assays.

Paired serum and saliva samples were tested by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) for the presence of human immunodeficiency virus (HIV) antibodies. The study group included 36 individuals known to be HIV seropositive and 14 healthy, seronegative controls. HIV antibodies were detected in all but one of the saliva samples of the seropositive subjects. In this particular patient, seroconversion was documented 1 week earlier by sequential testings. A further saliva sample obtained 2 months later was ELISA positive for salivary HIV antibodies. Antibodies against HIV proteins gp120 and gp160 were detected by Western blot assay in all saliva specimens taken from HIV seropositive subjects (including the ELISA-negative patient who seroconverted. Antibodies against other viral proteins (p65, p55, p51, gp41, p35, p24 p18) were found in saliva haphazardly without any clear-cut correlation with the clinical stage of the disease. Pretreatment of the saliva with protease inhibitor was essential for the diagnostic use of saliva for the detection of HIV antibodies by Western blot assay. Calculation of the ratio of titres in serum to those in saliva showed the highest ratios in symptomless subjects (mean +/- SD; 1844 +/- 1412) and the lowest in patients with acquired immune deficiency syndrome (AIDS) (mean +/- SD; 811 +/- 445). The ratio of serum to saliva by ELISA showed a positive correlation with salivary flow rate, indicating a dilution of salivary HIV antibodies with increasing salivary flow rate. The gingival bleeding index was negatively correlated with the ratio, supporting the concept that salivary HIV antibodies transudate from blood to saliva via gingival fluid.

Blotting, Western↗

Mild brain atrophy in early HIV infection: the lack of association with cognitive deficits and HIV-specific intrathecal immune response.

Brain MRI and/or CT were performed on 72 HIV-infected patients at various stages of the disease, and on 34 controls. The neuroradiological findings were related to duration of the infection, neurological symptoms, and cognitive abnormalities as well as to immunological findings in the CSF and blood. All types of brain atrophy were more severe and more frequent in HIV-infected subjects than in controls. Patients with neurological symptoms, those with advanced HIV infection, and patients with a duration of HIV infection of more than 4 years showed the most severe and most frequent neuroradiological abnormalities, including central and cortical atrophy, brain stem atrophy, and cerebellar atrophy. Subjects with cognitive defects exhibited more severe central atrophy than cognitively intact patients. However, slight brain atrophy and/or parenchymal lesions were found in 57% of cognitively intact HIV-seropositive individuals. Patients with brain atrophy and those with radiologically normal brain, both showed increased intrathecal synthesis of total IgG, and intrathecal HIV-antibody synthesis. However, a declined general immune response and a lowered CSF leukocyte count were seen predominantly in patients with brain atrophy. The results suggest that subcortical, neurologically "silent" areas of brain white matter are an early target of HIV infection.

AIDS Dementia Complex↗

Antibodies to recombinant HIV-1 nef protein detected in HIV-1 infection as well as in nonrisk individuals.

Antibodies to the human immunodeficiency virus (HIV) regulatory gene nef (negative factor) product are claimed to be characteristic of early and latent HIV infection. We looked for anti-nef antibodies in individuals infected with HIV or at risk for HIV, in blood donors, and in patients with diverse dermatological disorders. In HIV-infected patients, antibodies to recombinant nef protein were seen by Western blot assay in 29 of 54 (54%) individuals at any time during a prospective follow-up. Except for a decline in the level prior to ARC and AIDS, the occurrence of antibodies did not significantly correlate with any pattern of disease progression in 22 patients followed for up to 4 years. Among the 141 HIV risk group members, negative in recombinant HIV ELISA tests, anti-nef antibodies were detected in 7 (5%) individuals. However, an anti-nef antibody response was also seen in 5 of 93 (5%) nonrisk dermatological patients and in 4 of 37 (11%) healthy blood donors. Solitary HIV gag protein antibody responses were most frequent (7%) in the group of individuals at risk for HIV but the majority of anti-nef positive sera did not react with HIV gag proteins. The relatively frequent occurrence of indistinguishable anti-nef antibody responses in nonrisk individuals suggests that immunological cross-reaction between nef and some cellular regulatory protein may occur.

Female↗

CSF and serum beta-2-microglobulin in HIV infection related to neurological dysfunction.

Elevated (greater than 2.2 mg/l) CSF beta-2-microglobulin (beta 2m) level was found in 9 of 16 neurologically symptomatic patients but in only 4 of 21 who were neurologically symptom-free (P less than 0.01). Serum beta 2m concentration was elevated (greater than 2.5 mg/l) in 12 of 16 neurologically symptomatic patients but in only 8 of 21 symptom-free patients (P less than 0.01). When the CSF and serum beta 2m levels were related to various stages of HIV infection, the highest mean values for both CSF and serum were found in patients with acquired immunodeficiency syndrome (AIDS), followed by lower values in AIDS-related complex (ARC), lymphadenopathy syndrome (LAS), and asymptomatic seropositive individuals (ASX), in decreasing order of preference. Our results suggest that elevated beta 2m in CSF and serum is related to the stage of general HIV infection and that elevated CSF beta 2m in the presence of intact BBB may be useful in evaluating CNS involvement in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

[HIV/AIDS today].

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AIDS Serodiagnosis↗

Oral candidal infection as a sign of HIV infection in homosexual men.

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.

Alcohol Drinking↗

Cognitive changes as early signs of HIV infection.

Neuropsychological examination was performed on 13 patients and 10 matched controls to assess the brain involvement of patients with human immunodeficiency virus (HIV) infection. HIV-infected patients showed a significant decline in visuomotor, visuoconstructive and practical abilities as well as in motor-free visuospatial performance and repeating a long sentence. These findings could not be explained by the concomitant mental depression of these patients. Neither were they associated with any particular stage of HIV infection. The results suggest that mild cognitive changes may be detected even in the early stages of HIV infection, when examined by appropriate neuropsychological methods.

Acquired Immunodeficiency Syndrome↗

Intrathecal humoral immunologic response in neurologically symptomatic and asymptomatic patients with human immunodeficiency virus infection.

We analyzed the intrathecal humoral immunologic response in 42 human immunodeficiency virus (HIV)-infected patients. Eighteen patients had clinical neurologic abnormalities, while the remaining 24 patients were neurologically symptom-free. Nine of the neurologically symptomatic patients at early infection had slight neurologic dysfunction; in nine other subjects at late infection, the neurologic impairment was moderate or severe. When compared with symptom-free patients, neurologically symptomatic patients had increased intra-blood-brain barrier (BBB) HIV-specific IgG (p less than 0.001) and total IgG synthesis (p less than 0.01) with oligoclonal bands (OCBs) in the CSF and/or serum (11/18 versus 3/24). At early stages of the infection, neurologically symptomatic patients showed increased total intrathecal IgG synthesis (9/9) coincident with OCBs in the CSF and serum (7/9) and slight mononuclear pleocytosis (7/9), but less frequent HIV-specific IgG production within the CNS (6/9). In advanced infection, the number of neurologically symptomatic patients with intrathecal HIV-specific IgG synthesis (8/9) was higher, while the number of those with increased total intra-BBB IgG synthesis (5/9; p less than 0.01), OCBs (4/9), and increased CSF leukocyte count (1/9; p less than 0.001) was lower than at early infection. Our data suggest humoral intra-BBB immunoactivation at early stages of HIV infection followed by declining B cell response within the CNS at advanced infection.

Acquired Immunodeficiency Syndrome↗