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Biomedical subjects

R C Gallo

Publications and source records attributed to R C Gallo.

At least 307 records · Page 17Linked to original sources
PubMed1987

Complete nucleotide sequences of functional clones of the AIDS virus.

To examine the mechanism of lymphocytotoxicity induced by human T-lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV), an in vitro model has been developed. Introduction of an HTLV-III/LAV proviral clone, HXB2, into normal lymphocytes results in the production of virions and cell death. The complete nucleotide sequence of the proviral form of HXB2 has now been determined. Its structure is quite similar to that previously determined for HTLV-III/LAV clones whose biological capacities had not previously been demonstrated. The biological function of two additional clones of HTLV-III/LAV, BH10 and HXB3, are reported. Clone BH10 which lacks the 5' long terminal repeat sequences (LTR) and a portion of the 3' LTR is reconstituted by substituting the corresponding sequences of HXB2 and is shown to be capable of generating infectious cytopathic virions. Clone HXB3, which has been partially sequenced, is also found to be capable of producing lymphocytopathic virus. Clone HXB3 differs from HXB2 in its lack of a termination codon in 3' orf, demonstrating that 3' orf plays no major role in virus replication or cytopathic activity. These data provide the necessary background to allow the identification of viral determinants of replication, cytopathic activity, and antigenicity using these functional proviral clones.

Base Sequence↗
PubMed1987

Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions.

Independent isolates of human immunodeficiency virus (HIV) exhibit a striking genomic diversity, most of which is located in the viral envelope gene. Since this property of the HIV group of viruses may play an important role in the pathobiology of the virus, we analyzed the predicted amino acid sequences of the envelope proteins of seven different HIV strains, three of which represent sequential isolates from a single patient. By using a computer program that predicts the secondary protein structure and superimposes values for hydrophilicity, surface probability, and flexibility, we identified several potential antigenic epitopes in the envelope proteins of the seven different viruses. Interestingly, the majority of the predicted epitopes in the exterior envelope protein (gp120) were found in regions of high sequence variability which are interspersed with highly conserved regions among the independent viral isolates. A comparison of the sequential viral isolates revealed that changes concerning the secondary structure of the protein occurred only in regions which were predicted to be antigenic, predominantly in highly variable regions. The membrane-associated protein gp41 contains no highly variable regions; about 80% of the amino acids were found to be conserved, and only one hydrophilic area was identified as likely to be accessible to antibody recognition. These findings give insight into the secondary and possible tertiary structure of variant HIV envelope proteins and should facilitate experimental approaches directed toward the identification and fine mapping of HIV envelope proteins.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Relationship between HTLV-III neutralizing antibody and clinical status of pediatric acquired immunodeficiency syndrome (AIDS) and AIDS-related complex cases.

To investigate a possible protective role of HTLV-III neutralizing antibodies in individuals exposed to the virus, sera of children with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex were analyzed for neutralizability of HTLV-IIIB infectivity. Twelve pediatric patients (nine acquired immunodeficiency syndrome, three acquired immunodeficiency syndrome-related complex) were clinically stable and had survived more than 2 yr postonset. Their predominant clinical problems included lymphocytic interstitial pneumonia, candidiasis, recurrent bacterial infections, failure to thrive, and lymphadenopathy. Twelve additional children (all acquired immunodeficiency syndrome) were classified as clinically poor; 10 of them had died. Their median length of survival was less than 2 yr, and their disease spectrum included progressive encephalopathy, thymic depletion or atrophy, and Pneumocystis carinii pneumonia in addition to many of the clinical features of the stable children. All (100%) of the stable patients possessed serum neutralizing antibody in contrast to only one of the 12 (8%) clinically poor patients. A simple decline in immunologic reactivity to HTLV-III antigens with disease progression did not account for this difference, since HTLV-III antibody titers of the clinically poor cases (1 X 10(2) to 1 X 10(7)) ranged as high as those of the stable cases (1 X 10(4) to 1 X 10(7)) when measured by the ELISA technique. Although stable cases possessed a higher geometric mean titer (2.8 X 10(5)) by ELISA than the poor cases (4 X 10(4)), this difference was not statistically significant. Serial serum samples from stable children exhibited continual neutralizing antibody activity while two of three clinically poor cases lacked neutralizing activity in serial specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗
PubMed1987

Ultrastructural characterization of a new human B lymphotropic DNA virus (human herpesvirus 6) isolated from patients with lymphoproliferative disease.

A new DNA virus, designated "human B lymphotropic virus" or "human herpesvirus 6" (HBLV), has been isolated from the peripheral blood leukocytes of patients with various lymphoproliferative disorders, in some instances also associated with human immunodeficiency virus (HIV-1) infection. HBLV, propagated in vitro in human cord blood lymphocytes, was found to be ultrastructurally similar to members of the herpesvirus family. It is an enveloped virus with an icosahedral nucleocapsid made up of 162 capsomeres. Unenveloped nucleocapsids in the cytoplasm wee always coated with a tegument, a feature also described for human cytomegalovirus (HCMV). However, the nucleoprotein core of HBLV does not have the beaded appearance as that of HCMV, nor do HBLV-infected cells contain the skein-like structure. Immune electron microscopy demonstrated the presence of specific antibodies to viral envelope and internal antigens in sera of infected patients, indicating that this virus is a possible human pathogen. These and previously reported characteristics are consistent with the HBLV being a new and unique DNA virus morphologically belonging to the herpesvirus family.

Cytomegalovirus↗
PubMed1987

Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro.

Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord-blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.

Adolescent↗
PubMed1987

Mechanism of leukemogenesis by human T-cell leukemia virus types I and II: role of the lor gene.

The human T-cell leukemia (HTLV) family of viruses now include two groups of transforming viruses (HTLV-I and HTLV-II) and one group of viruses with immunosuppressive activity but no apparent transforming ability (HTLV-III). Nucleotide sequence analysis of an HTLV-I provirus by Seiki et al [Proc Natl Acad Sci USA 1982: 6899-902] has revealed a distinct region of the genome located between env and the long terminal repeat sequences (LTR). Analysis of a variant of HTLV-I, called HTLV-Ib, which retains transforming ability, revealed a deletion in the 5' portion of this sequence that indicates that this portion of the sequence probably does not play an essential role in transformation. Hybridizations at varying stringencies show that at least a portion of this additional region of HTLV-I and -II is more highly conserved than most other regions of the genome. The DNA sequence of this HTLV-II region localizes the area of homology within the 1,000 base pairs just upstream of the LTR; the remainder of the region is not conserved. The conserved region includes a long open reading frame, is denoted lor, and has the coding capacity for a protein of at least 38 kilodaltons (kd). Studies of the transcriptional activity of the LTR sequences show that the rate of LTR-directed transcription is greatly augmented in HTLV-infected cells, a phenomenon called trans-acting transcriptional regulation. It is suggested that transformation of lymphocytes by HTLV-I or -II is mediated by action of HTLV-encoded trans-acting transcription factors on cellular genes that control the replication of lymphocytes.

Deltaretrovirus Infections↗
PubMed1987

Differential susceptibility of human mononuclear cells to infection with HTLV-I.

Infection with human T-cell leukaemia/lymphoma (HTLV-I) preferentially affects T cells of the OKT-4 phenotype. The aim of the present study was to determine whether distinct T-cell subsets exhibit differences in susceptibility to virus infection. T cells from peripheral blood were separated according to cell densities by 7-step Percoll gradients. Separated T-cell subpopulations were infected with HTLV-I, using cocultivation with irradiated virus producer MT-2 cell line. Percentages of HTLV-I-infected cells and their phenotypes were assayed by immunofluorescence assay (IFA), using highly specific mouse monoclonal antibody directed against HTLV-I P-19 core protein, and other surface markers. The results showed that different T-cell subpopulations were susceptible to HTLV-I infection with the exception of large granular lymphocytes (LGL) which exhibit high cell-mediated natural cytotoxicity (CMNC).

Adult↗
PubMed1987

The AIDS virus.

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Acquired Immunodeficiency Syndrome↗