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F Chiodi

Publications and source records attributed to F Chiodi.

At least 55 records · Page 3Linked to original sources
PubMed1992

Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro.

A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their ability to neutralize MN and IIIB strains of the virus. Neutralization was determined as the ability of the Fab fragments to inhibit infection as measured in both a p24 ELISA and a syncytium-formation assay. One group of closely sequence-related Fab fragments was found to neutralize virus in both assays with a 50% neutralization titer at approximately 1 micrograms/ml. Another Fab neutralized in the p24 ELISA but not in the syncytium assay. The other Fab fragments showed weak or no neutralizing ability. The results imply that virion aggregation or crosslinking of gp120 molecules on the virion surface is not an absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments were shown to be competitive with soluble CD4 for binding to gp120 and yet few neutralized the virus effectively, implying that the mechanism of neutralization in this case may not involve receptor blocking. The observation of a preponderance of high-affinity Fab fragments with poor or no neutralizing ability could have implications for vaccine strategies.

Amino Acid Sequence↗
PubMed1992

Lack of autologous neutralizing antibodies in the cerebrospinal fluid of HIV-1 infected individuals.

The cerebrospinal fluids (CSF) and sera from HIV-1-infected individuals at different clinical stages were monitored for neutralizing activity against CSF-derived HIV-1 isolates. None of the CSF samples and only one of seven serum samples could neutralize the autologous CSF isolate. CSF samples collected one to two years later from the same patients also lacked autologous neutralizing antibodies against these isolates. However, some CSF samples were able to neutralize heterologous CSF isolates albeit in low titers. HIV antibody positive control sera could readily neutralize all of the CSF isolates demonstrating that these isolates were not resistant to neutralization per se. IgG antibodies against the HIV-1 envelope protein and, specifically, against the V3 loop of HIV-1 gp120 (MN) were present in some CSF samples, although the samples lacked neutralizing activity. In summary, this study demonstrates a lack of autologous neutralizing antibodies in CSF samples when assayed against CSF-derived HIV-1 isolates.

Amino Acid Sequence↗
PubMed1992

Four distinct antigenic regions are present in the primary structure of HIV-1 and HIV-2 proteinases.

OBJECTIVE: The purpose of this study was to assay reactivity of antibody-positive sera to different parts of the HIV-1 and HIV-2 proteinase (PR) proteins. DESIGN: Since the majority of HIV-1-antibody-positive sera react to the proteinase, but the antigenic determinants on the protein have not been identified, we attempted to identify these determinants. INTERVENTIONS: We synthesized 18 peptides representing the PR of HIV-1 and HIV-2 in order to map serum reactivity to the PR protein. RESULTS: Both HIV-1- and HIV-2-antibody-positive sera recognized four distinct antigenic regions in the HIV-1 and HIV-2 PR. CONCLUSIONS: Correlation between our results and the crystallographic structure of the protein revealed that the antigenic regions are positioned at the surface of the HIV-1 PR. Although the structure of HIV-2 PR has not yet been characterized, our results indicate that the folding of the HIV-1 and HIV-2 PR may be very similar.

Amino Acid Sequence↗
PubMed1992

Human immunodeficiency virus type 1 is present in the cerebrospinal fluid of a majority of infected individuals.

Cerebrospinal fluid (CSF) specimens from 63 patients with different severities of human immunodeficiency virus (HIV-1) infection, including asymptomatic virus carriers, were examined for the presence of HIV-1 by using polymerase chain reaction (PCR) and virus isolation. Polyadenylated RNA, presumably associated with virus particles, was extracted and reverse transcribed, and the pol region was amplified in a nested PCR. Virus could be detected in 90% of the CSF specimens examined by PCR, and data on isolation of virus from CSF were in agreement with these figures. In fact, when several CSF specimens from the same individual were studied, HIV-1 could be isolated from 80% of the patients. The presence of the viral RNA in CSF was independent of the clinical stage of infection and of neurological symptoms. These results show that the spread of HIV-1 to the brain represents an early event during infection and occurs in the majority of asymptomatic individuals.

Blood↗
PubMed1991

Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity.

Twenty-five 13- to 35-amino-acid-long peptides representing regions of human immunodeficiency virus type 2 (HIV-2), strain SBL6669, envelope proteins were evaluated for their immunogenic activity in guinea pigs. The peptides were selected to provide homologous representation of sites in the HIV-1 envelope proteins that were previously documented to have a particular immunogenic importance. A number of the HIV-2 peptides were found to be capable of inducing strain SBL6669 neutralizing and antibody-dependent cellular cytotoxicity (ADCC) antibodies. Two overlapping peptides covering amino acids 311-337 representing the central and C-terminal part of the variable third (V3) region, terminology according to Modrow et al. [Modrow, S., Hahn, B., Shaw, G. M., Gallo, R. C., Wong-Staal, F. & Wolf, H. (1987) J. Virol. 61, 570-578], showed the most pronounced capacity to induce neutralizing antibodies. One of the peptides (amino acids 318-337) also induced antibodies mediating ADCC. Two additional regions in the large glycoprotein, gp125, containing linear sites reacting with neutralizing antibodies were identified (amino acids, 119-137 and 472-509). The transmembrane protein, gp36, of HIV-2 harbored two regions of importance for induction of neutralizing antibodies (amino acids 595-614 and 714-729). ADCC activity was induced by two additional gp125-specific peptides (amino acids 291-311 and 446-461). Thus, except for the single V3-specific site there was no correlation between linear immunogenic sites stimulating neutralizing antibody and ADCC activity. These findings pave the way for development of synthetic vaccines against HIV-2 and possibly also simian immunodeficiency virus infections. The capacity of such a product to induce protective immunity can be evaluated in macaque monkeys.

Amino Acid Sequence↗
PubMed1991

Brain-derived cells can be infected with HIV isolates derived from both blood and brain.

HIV type 1 and 2 isolates derived from brain and blood of infected individuals were used to infect astrocytic cells of tumor origin. Infection was monitored by polymerase chain reaction. The majority of the isolates infected the glioma cells, independently of the source of isolation. Added to the fact that the majority of primary HIV isolates infect cells of the monocyte/macrophage lineage, these results indicate that primary blood and brain HIV strains have similar target cells. The production of virus from infected astrocytes was detected only upon infection with two macrophage-adapted strains. Also in this case, the number of infected cells was very low and only one in 5000 cells carried the proviral HIV genome.

Blood↗
PubMed1991

Simian immunodeficiency virus (SIVsm) isolation from blood and brain of experimentally infected macaques.

The possibility of using simian immunodeficiency virus (SIV)-infected macaques to study pathogenic events linked to HIV infection of the brain prompted us to investigate some of the virological features in SIV-infected macaques. Nine cynomolgus macaques were inoculated with SIVsm and killed at different times. We successfully isolated virus from the blood of all the animals and from the brains of eight. These results point to the early and regular spread of this lentivirus to the brain. Neutralizing activity was studied in the serum and cerebrospinal fluid specimens obtained from these macaques against a selected group of isolates. Cerebrospinal fluid did not show any neutralizing activity. Our findings integrate the observations from HIV-1 infection in man and indicate that SIV infection of macaques is a useful model for studying pathogenic events of brain infection.

Animals↗
PubMed1991

Neurotropism of human immunodeficiency virus.

Three major characteristics of human immunodeficiency virus (HIV) infection define HIV as neurotropic. 1) Clinically, distinct neurological syndromes are associated with HIV infection and 2) presence of the virus as well as 3) pathological changes can be demonstrated in the central nervous system. Spread of HIV to the brain seems to be the general rule. Virus expression appears to be restricted during the asymptomatic period but increases with severity of HIV infection. Whether this reflects the emergence of virus variants with increased replicative capacity in brain cells has yet to be elucidated.

AIDS Dementia Complex↗
PubMed1991

Identification of a uniquely immunodominant, cross-reacting site in the human immunodeficiency virus endonuclease protein.

One of the features of the life cycle of retroviruses is insertion of the proviral DNA into host chromosomes. A protein encoded by the 3' end of the pol gene of the virus genome has been shown to possess endonuclease activity (D. P. Grandgenett, A. C. Vora, and R. D. Schiff, Virology 89:119-132, 1978), which is necessary for DNA integration. Sera from the majority of human immunodeficiency virus (HIV)-infected individuals react with endonuclease protein p31 in serological tests (J. S. Allan, J. E. Coligan, T.-H. Lee, F. Barin, P. J. Kanki, S. M'Boup, M. F. McLane, J. E. Groopman, and M. Essex, Blood 69:331-333, 1987; E. F. Lillehoj, F. H. R. Salazar, R. J. Mervis, M. G. Raum, H. W. Chan, N. Ahmad, and S. Venkatesan, J. Virol. 62:3053-3058, 1988; K. S. Steimer, K. W. Higgins, M. A. Powers, J. C. Stephans, A. Gyenes, G. George-Nascimento, P. A. Liciw, P. J. Barr, R. A. Hallewell, and R. Sanchez-Pescador, J. Virol. 58:9-16, 1986). It is not known, however, which part of the protein represents the target(s) for antibody response. To study this, we synthesized peptides and used them in an enzyme-linked immunosorbent assay system to map the reactivity of human immunodeficiency virus type 1 (HIV-1) antibody-positive sera to the different regions of the HIV endonuclease. A uniquely antigenic, HIV-1- and HIV-2-cross-reacting site was identified in the central part of this protein from Phe-663 to Trp-670.

Amino Acid Sequence↗
PubMed1991

Effect of zidovudine on cerebrospinal fluid in patients with HIV infection and acute neurological disease.

Two cases of HIV infection associated with neurological complications are described. The patients had been followed with repeated cerebrospinal fluid (CSF) analyses 1-3 years before the neurological disease and 5 months after zidovudine treatment. CSF mononuclear cell count and the AIDS predictors beta 2-microglobulin and neopterin decreased in CSF after treatment and were lower or at the level seen 1-3 years before treatment. The results suggest that zidovudine has a suppressive effect on the HIV infection in CNS at least for 5 months, even when low zidovudine doses (500 mg daily) were used.

AIDS Dementia Complex↗
PubMed1990

Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system.

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients at different stages of human immunodeficiency (HIV) virus infection and of patients with multiple sclerosis (MS) or other inflammatory (OID) and noninflammatory neurological diseases (OND). In the advanced stages of HIV infection and in OID, IL-6 was detected more frequently (80 and 75% of the cases) and at higher concentrations than in the early stages of HIV infection. MS and OND (44, 48, and 44% of cases). Analysis of CSF and paired sera indicated that IL-6 production can be compartmentalized to either of the fluids. Evidence that altered blood-brain barrier functions can, at least in part, influence the CSF IL-6 levels was found in OID patients. No association was evident between intrathecal immunoglobulin synthesis and CSF IL-6 levels. Interleukin-1 (IL-1) levels were detectable in a minority of the samples from neurological patients; one OID patient had high levels of both CSF IL-1 and IL-6.

Cerebral Infarction↗
PubMed1989

IgG subclass responses to a transmembrane protein (gp41) peptide in HIV infection.

The IgG subclass distribution to the E34/E32 peptides, derived from the HIV-1 glycoprotein 41 transmembrane protein, was analyzed in ELISA. Sera from individuals at different stages of the disease were assayed. A restricted subclass response of mainly IgG1 and IgG2 was found. The subclass response was of a different type than the one observed to HIV whole Ag and to a synthetic peptide from the C'-terminal part of the HIV-1 p24 core protein. An increased subclass restriction was observed in progressed stages of the disease.

Amino Acid Sequence↗
PubMed1989

Screening of African sera stored for more than 17 years for HIV antibodies by site-directed serology.

Antibodies to Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) were investigated, using site-directed enzyme immunoassay (ELISA), in 320 specimens obtained from three remote, African tribes during 1969-1971. Using HIV-1 E34/E32 ELISA and HIV-2 149 ELISA, assay were conducted on 101 serum specimens from the Korekore tribe of Zimbabwe, 93 specimens from the Mano tribe of Liberia, and 126 specimens from the Turkana tribe of Kenya; specimens which tested positive in ELISA were further tested by radioimmunoprecipitation assay (RIPA) and Western blot (WB). Two serum specimens from the Mano tribe of Liberia gave OD 492 nm values greater than 0.2 in HIV E34/E32 ELISA in all three runs. These two specimens reacted with HIV-1 envelope proteins gp160 and gp120 and the internal protein p24 in RIPA and WB; however, the reactivity was uncostant. All other serum specimens were negative for HIV-1 and HIV-2 antibodies. Site directed ELISA serology for HIV-1 and HIV-2 gave very low rates of false positive reactivity. Thus, reaction with HIV-1 antigen was identified in two persons of one tribe in Liberia in 1971, but HIV-2 antibodies were not detected in this tribe; HIV-1 and HIV-2 antibodies were absent during the late 1960's and early 1970's from two African tribes resident in Zimbabwe and Kenya.

AIDS Serodiagnosis↗
PubMed1989

Biological characterization of paired human immunodeficiency virus type 1 isolates from blood and cerebrospinal fluid.

Virus has been isolated from the blood and cerebrospinal fluid (CSF) of eight subjects with varying severity of human immunodeficiency virus type 1 (HIV-1) infection and from the frontal lobe of one patient with AIDS. The five patients with AIDS-related complex (ARC) and AIDS also showed neurological/psychiatric complications. With the exception of one isolate from the CSF of an asymptomatic carrier, all isolates replicated in peripheral blood mononuclear cells and monocytes after cell-free transmission. Isolates obtained from the blood of patients in late stages of HIV infection replicated in 3 (of 4) cases in H9 cells, whereas none of the blood isolates from patients in the early stages did so. The capacity of CSF isolates to replicate in H9 cells was low (only 2 of 12). Paired virus isolates from blood and CSF of the same patient could be distinguished by their replicative capacity in different cell lines, type of cytopathic effect, and protein profile as tested by radioimmunoprecipitation. The results indicate that variant viruses with distinct biological characteristics may be isolated from the blood and CSF of the same patient.

AIDS Dementia Complex↗
PubMed1989

HIV-1-specific antibodies in cerebrospinal fluid mediate cellular cytotoxicity and neutralization.

Antibodies mediating HIV-1-specific cellular cytotoxicity (ADCC) and virus neutralizing activity were detected in the cerebrospinal fluid (CSF) and, as previously reported, in sera of subjects with varying severity of HIV-1 infection, including patients with or without neurologic or psychiatric symptoms. ADCC-mediating antibodies against target cells infected with the HTLV-IIIB strain of HIV-1 were less frequently present in CSF than in sera, 32 and 60%, respectively. The frequency of ADCC-positive CSF was comparable for the different clinical stages of the disease and was apparently not influenced by the presence or absence of neurologic/psychiatric symptoms. Virus-neutralizing activity was tested against HTLV-IIIB and one CSF-derived viral isolate. Serum antibodies neutralized HTLV-IIIB more frequently than the CSF isolate, 53 and 35%, respectively. In contrast, only three (7%) of the CSF specimens contained neutralizing activity to the CSF-derived isolate and none to HTLV-IIIB. Despite an intact blood-brain barrier in many subjects, the serum/CSF ratios of ADCC or neutralizing antibodies were lower than normally expected. This indicates that both ADCC-mediating and virus neutralizing antibodies may be intrathecally synthesized. Whether these antibodies are protective against or contribute to the histopathologic changes in the brain is not known at present.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1.

Neopterin, a biochemical marker for the activation of cell-mediated immune reactions, was determined in serum and cerebrospinal fluid (CSF) from patients infected with HIV-1. A significant correlation was found between serum and CSF neopterin concentrations, although concentrations of neopterin in serum were more closely correlated with the clinical severity of HIV-1 infection than those in CSF. However, higher CSF levels were observed in patients with neurologic/psychiatric symptoms than in unaffected patients. Also, quotients of CSF neopterin versus serum neopterin concentrations were increased, indicating intrathecal production of neopterin. Positive HIV-1 isolation from peripheral blood mononuclear cells (PBMC) was associated with higher neopterin concentrations in serum, when compared with negative HIV-1 isolation. Neopterin in CSF appears to be a suitable biochemical marker in patients with HIV-1 infection for detecting overt neurologic/psychiatric disturbances. The data suggest that in HIV-1 infected patients, cell-mediated immune reactions might be activated intrathecally and might contribute to neuropsychiatric disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Enhancement of human immunodeficiency virus (HIV) replication in human monocytes by low titres of anti-HIV antibodies in vitro.

Low concentrations of serum obtained from a patient with acquired immunodeficiency syndrome (AIDS) enhanced the replication of human immunodeficiency virus type 1 (HIV-1) in a particular subclone of the CD-4-positive monocytoid cell line U937 clone 2. Cells of this subclone have a high expression of Fc receptors and a considerable degree of Fc-mediated phagocytic activity. IgG purified from the serum was also able to enhance the replication. These results indicate that low concentrations of human anti-HIV antibody may enhance HIV replication on human monocyte-macrophages. Furthermore, two mouse IgG1 monoclonal antibodies against gp120, the envelope glycoprotein of HIV-1, also induced enhancement at low concentrations. The binding of radiolabelled gp120 to the cells was increased at the same low concentrations. Antibodies against envelope glycoproteins may cause enhancement of HIV infection. Both normal and enhanced replication of HIV were completely inhibited by the masking of the binding site of CD4 molecules with F(ab')2 fragments of anti-CD4 antibody. Moreover, CD4-positive, Fc gamma RI-negative K562 cells and mouse macrophages failed to show any infection in the presence of antibody. These results suggest that CD4 molecules on the cell surface are necessary to cause enhancement of infection of HIV on monocyte-macrophages.

Acquired Immunodeficiency Syndrome↗