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R C Gallo

Publications and source records attributed to R C Gallo.

At least 271 records · Page 15Linked to original sources
PubMed1988

Human immunodeficiency virus type 2 long terminal repeat: analysis of regulatory elements.

The long terminal repeats (LTRs) of the human immunodeficiency virus type 2 (HIV-2) and a related simian immunodeficiency virus (SIVmac) contain cis-acting positive regulatory elements upstream and the major transactivator gene (tat) response element and a possible negative regulatory element downstream of the transcriptional initiation site. The tat response element of HIV-2 and of SIVmac was more complex than that of HIV-1. Two structurally similar subelements within the HIV-2 tat response element could be identified. Both of these subelements were required for optimal transactivation by the HIV-2 tat gene product. Either of these subelements, however, was sufficient for transactivation by the HIV-1 tat gene product. These observations provide an explanation for the poor transactivation of HIV-1 LTR-directed gene expression by the HIV-2 tat gene product since the HIV-1 LTR contains an analog of only one of the HIV-2 subelements. The HIV-2 tat gene product also affected the function of the upstream elements, including enhancer activity. The response of these cis elements of HIV-2 to transactivation by HIV-2/SIVmac and HIV-1 tat gene differed somewhat in virus-infected and tat gene transfected cells, probably related to the differences in the effective concentration of the tat gene products and/or other viral or cellular factors. The steady-state levels of HIV-2 LTR-linked gene transcripts were much higher in the presence of HIV-2, SIVmac, and HIV-1 tat genes than in their absence, suggesting transcriptional modulation as a mechanism for tat gene function.

Base Sequence↗
PubMed1988

Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120.

Antisera to recombinant human immunodeficiency virus (HIV) proteins containing the entire envelope, gp160, or the central portion of the envelope, PB1, can inhibit fusion of virally infected cells in culture. This fusion inhibition is HIV-variant specific--that is, anti-gp160-IIIB inhibits fusion of isolate HTLV-IIIB-infected cells but not of isolate HTLV-IIIRF-infected cells. Both anti-gp160 and anti-PB1 are completely blocked in fusion inhibition activity by the addition of PB1 protein. A 24-amino acid peptide (RP135, amino acids 307-330) completely blocks fusion inhibition activity of both antisera and also blocks the activity of serum from a chimpanzee infected with HTLV-IIIB. Thus, the principal epitope that elicits fusion-inhibiting antibodies is located in the central portion of gp120.

Amino Acid Sequence↗
PubMed1988

Nucleotide sequence analysis of the env gene of a new Zairian isolate of HIV-1.

As a further step in the continuing process of defining the extent and nature of variability of the envelope (env) gene of HIV-1, we have cloned a new Zairian isolate, JY1, and sequenced the env gene of this isolate. Although the restriction map of the env region of JY1 was found to be more similar to that of the American prototype, BH10, than maps of all previously reported Zairian isolates and some American isolates, nucleotide sequencing of the JY1 env gene showed that it is among the most divergent from BH10 yet reported and that it differs from previously reported Zairian isolates almost to the same extent that it differs from BH10. A typical pattern of variable and constant regions was seen. A number of complex duplications were found in the hypervariable regions of JY1. The unique and highly divergent nature of the env gene of JY1 enhances its usefulness as part of a panel of HIV-1 isolates being evaluated in biologic and immunologic studies toward vaccine development.

Amino Acid Sequence↗
PubMed1988

High prevalence of serum antibodies to reverse transcriptase in HIV-1-infected individuals.

The HIV immunoblot profiles of 700 HIV-antibody-positive sera were examined to determine the frequency of antibody reactivity with p66/p51, the reverse transcriptase of HIV. We report a remarkably high seroprevalence of antibodies to p66/p51, detected in 79% of the sera. Only gp41 is recognized more frequently in these assays. The level of anti-p66/p51 seroreactivity varies only slightly among the clinical stages of HIV infection.

AIDS-Related Complex↗
PubMed1988

B and T cell reactivities after immunization of macaques with HIV subcomponents.

A model system was established for studies of humoral and cellular immunity to human immunodeficiency virus (HIV) antigens after vaccination. Macaques (Macaca fascicularis) were immunized with purified HIV, an infected cell extract rich in gp120 or polypeptides of cloned genes representing parts of p24, gp41, and gp120. Western blot analysis best showed the appearance of antibodies to nucleocapsid proteins, and antibodies to higher molecular weight envelope glycoproteins were better demonstrated by radioimmunoprecipitation. With whole HIV, antibodies to p24 appeared first, and sometimes were the only ones to be demonstrable. Several immunizations with HIV or recombinant polypeptides were required to obtain antibodies to gp120, and the responses were weak. Although the envelope-specific response was weak, this was the only component that mediated neutralizing capacity. Escherichia coli-derived viral transmembrane polypeptide (g)p41 also had a poor immunizing effect. IgG synthesis from B cells in vitro was demonstrable to antigens and generally paralleled the antibody titers of sera after multiple immunizations. The HIV-specific lymphocyte proliferation response as measured by DNA synthesis was best seen with polypeptide p24-15, followed by the other antigens.

Animals↗
PubMed1988

A unique human immunodeficiency virus culture secreting soluble gp160.

A clone of the HUT78 cell line, chronically infected with the HIV-1 isolate HTLV-III451, has been demonstrated to secrete unprocessed HIV-1 envelope precursor protein gp160 as well as mature gp120. Further, when grown in serum-free defined medium these cells released approximately five times the amount of virus compared with cultures in normal medium. These proteins corresponded in their immunologic reactivities with the respective envelope proteins of the HTLV-IIIB isolate. They formed high-affinity soluble complexes with the CD4 antigen and inhibited the syncytium formation induced by HTLV-IIIB on CD4-positive cells. This is the first description of an HIV-1 culture system capable of shedding into the medium native gp160 that is soluble in the absence of detergents.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Spectrum of HIV-1 neutralizing antibodies in a cohort of homosexual men: results of a 6 year prospective study.

Serum samples collected prospectively between 1982 and 1987 from a cohort of homosexual men were analyzed for HIV-1 neutralizing antibodies. Seven seroconverters who became infected between 1982 and 1984 and 12 seroprevalents who were already seropositive in 1982 remained free of AIDS. During the 6 year period, 1 seroconverter and 14 seroprevalents developed AIDS. Healthy seroconverters developed neutralizing antibodies slowly and reached moderate geometric mean titers (GMT) of 1:100 within 3 years of seroconversion. Healthy seroprevalents already had moderate titers in 1982, which increased markedly in 1985-1986 (GMT greater than 1:200) and subsequently returned to the previous level in 1987. Neutralizing antibody titers declined 3 years prior to diagnosis in men who developed AIDS and reached levels significantly lower than those of healthy counterparts 2 years before diagnosis. Analysis of neutralizing antibody activity to several HIV-1 isolates indicated that the lower titers of men who developed AIDS were not due to diminished group-specific reactivity. Thus, high neutralizing antibody titers correlated with better clinical outcome, and low or decreasing neutralizing antibody titer signaled poor prognosis. Although naturally developing neutralizing antibodies may ultimately be inadequate in controlling disease progression, measures able to boost the neutralizing antibody titer of individuals already infected with the virus or to elicit high-titer neutralizing antibodies in individuals at risk may yet prove beneficial in controlling viral spread in vivo or in preventing new infection, presumably in concert with cellular immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV-1 expression by T8 lymphocytes after transfection.

Acquired immune deficiency syndrome (AIDS) is an immunosuppressive disease associated with the depletion of T4 lymphocytes. Recently, an HIV-1 genome was molecularly cloned and shown to be fully infectious in vitro by transfection experiments. In this study, we show that HIV-1 can be transfected into T4 and T8 lymphocyte subpopulations and viral proteins and infectious virus particles are observed in both short- and long-term cultures. In addition, transfected T8 cells can be maintained in culture for long periods without apparent cytopathic effect.

Antigens, Viral↗
PubMed1988

Biochemical and immunological analysis of human immunodeficiency virus gag gene products p17 and p24.

Human immunodeficiency virus (HIV) p24 was purified to homogeneity and subjected to NH2-terminal sequencing. The sequence determined perfectly corresponded to the amino acid sequence predicted from the nucleotide sequence of a middle portion of the HIV first open frame: the gag gene. Edman degradation of purified HIV p17 revealed instead a blocked NH2 terminus. Hybridomas secreting monoclonal antibodies to p24 and p17 were developed and used to immunologically characterize these two HIV gag gene products. They identified two gag precursor polyproteins in the cytoplasm of HIV-infected cells: Pr53gag, which corresponds to the primary translational product, and Pr39gag, which corresponds to an intermediate product of cleavage of Pr53gag. These monoclonal antibodies allowed us also to study posttranslational modification of HIV p24 and p17. p24 was found to be phosphorylated, which is a very unusual feature for a major retroviral core protein. p17 was found to be myristylated, as are all NH2-terminal gag proteins of the known human retroviruses.

Amino Acid Sequence↗
PubMed1988

Human retroviruses and herpes viruses: their role in immune dysfunctions and neoplasia.

Human retroviruses (HTLV-I, HTLV-II, HIV-1, and HIV-2) and some human herpes viruses (notably EBV and HHV-6 or HBLV) infect chiefly target cells of the immune system. They can alter function of these cells, leading to many side effects, including mild (HTLVs), transient (EBV, HHV-6), or profound (HIVs) immune impairment with the associated clinical consequences. The retroviruses can also cause injury to the central nervous system but the mechanisms are poorly understood. An almost opposite effect of all of these immunocytotropic viruses is their capacity to directly induce abnormal cell growth of their target cells or indirectly of other cells. In addition to their importance in human disease, studies of these viruses are helping to provide new insights into the molecular mechanisms of gene regulation, fundamental aspects of the immune system, and of the origin, cellular and molecular pathogenesis of human tumors.

Deltaretrovirus↗
PubMed1988

AIDS in 1988.

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Acquired Immunodeficiency Syndrome↗
PubMed1987

The sor gene of HIV-1 is required for efficient virus transmission in vitro.

The genome of the human immunodeficiency virus HIV-1 contains at least eight genes, of which three (sor, R, and 3' orf) have no known function. In this study, the role of the sor gene was examined by constructing a series of proviral genomes of HIV-1 that either lacked the coding sequences for sor or contained point mutations in sor. Analysis of four such mutants revealed that although each clone could generate morphologically normal virus particles upon transfection, the mutant viruses were limited in their capacity to establish stable infection. Virus derived from transfection of Cos-1 cells (OKT4-) with sor mutant proviral DNA's was resistant to transmission to OKT4+ "susceptible" cells under cell-free conditions, and was transmitted poorly by coculture. In contrast, virus derived from clones with an intact sor frame was readily propagated by either approach. Normal amounts of gag-, env-, and pol-derived proteins were produced by all four mutants and assays in both lymphoid and nonlymphoid cells indicated that their trans-activating capacity was intact and comparable with wild type. Thus the sor gene, although not absolutely required in HIV virion formation, influences virus transmission in vitro and is crucial in the efficient generation of infectious virus. The data also suggest that sor influences virus replication at a novel, post-translational stage and that its action is independent of the regulatory genes tat and trs.

Animals↗
PubMed1987

In vitro susceptibility of different human T-cell subpopulations and resistance of large granular lymphocytes to HTLV-I infection.

T4 subpopulation of T lymphocytes is the preferential target of infection with human T leukemia/lymphoma virus of subgroup I (HTLV-I). In this study we attempt to determine whether different T-cell subsets exhibit differences in susceptibility to virus infection. T cells from cord or peripheral blood were separated according to cell densities and T-cell surface markers by Percoll gradient and Sepharose anti-Fab immunoadsorbent affinity column (IAC), respectively. Separated T-cell subpopulations were infected with HTLV-I, by means of co-cultivation with irradiated virus producer cell lines (MT-2, TK). Percentages of HTLV-I-infected cells were assayed by immunofluorescence assay (IFA), using highly specific mouse monoclonal antibody (MAb) directed against HTLV-I p19 core protein. The results showed that different T-cell subpopulations separated either by Percoll or by IAC were susceptible to HTLV-I infection with the exception of large granular lymphocytes (LGL), which exhibit high cell-mediated natural cytotoxicity (CMNC). The susceptibility to HTLV-I infection of T cells with CMNC activity was further studied on established cell clones with LGL morphology. The results showed again that these cells were resistant to the virus infection. The present studies indicate that different T-cell subpopulations, irrespective of their size and of cell-surface markers, are susceptible to HTLV-I infection, with the exception of functionally mature LGL or of immortalized LGL clones.

Cell Separation↗
PubMed1987

HTLV-I--associated B-cell CLL: indirect role for retrovirus in leukemogenesis.

Serum containing antibodies to the human T-lymphotropic virus type I (HTLV-I) has been observed at a higher than expected frequency in patients with B-cell chronic lymphocytic leukemia (CLL) in an area endemic for HTLV-I. An attempt was made to determine whether the cells from patients with this leukemia were HTLV-I antigen-committed B cells that had undergone malignant transformation. Cells from two HTLV-I seropositive Jamaican patients with CLL were fused with a human B-lymphoblastoid cell line. The hybridoma cells that resulted from the fusion of CLL cells from patient I.C. produced an immunoglobulin (IgM) that reacted with the p24 gag protein from HTLV-I, HTLV-II, and HTLV-III (now referred to as HIV), but showed preferential reactivity with HTLV-I. The specific immunoglobulin gene rearrangement (IgM, kappa) in the CLL cell was demonstrated in the hybridoma cell line, indicating that the captured immunoglobulin was from the CLL cells. The IgM secreted by the fusion of CLL cells from patient L.L. reacted only with HTLV-I-infected cells and with the HTLV-I large envelope protein (gp61) on Western blots. The CLL cells from these patients appear to be a malignant transformation of an antigen-committed B cell responding to HTLV-I infection, suggesting an indirect role for this retrovirus in leukemogenesis.

Antibodies, Viral↗
PubMed1987

Transmission of HTLV-I and HIV among homosexual men in Trinidad.

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15% vs 2.4% in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19% of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

HTLV-III infection of EBV-genome-positive B-lymphoid cells with or without detectable T4 antigens.

The infection of a number of new and established B-cell lines by human T-cell lymphotropic virus III (HTLV-III) was investigated. The B lymphocytes differed in their expression of T4 antigens detected by specific monoclonal antibodies (MAbs) and the presence of Epstein Barr virus (EBV)-DNA or antigens. The presence of the EBV genome was the only requirement for infection of B-lymphocytes by HTLV-III, although its presence did not ensure infection. Two EBV genome and T4 antigen-positive B-cell lines, lacking EBV early antigens (EA) and viral capsid antigens (VCA), could be productively infected with no induction of known EBV antigens. Two other EBV genome-positive cell lines, lacking T4, EA, and VCA could also be infected. Another genome-positive cell line (P3HR-I) that was EBV-EA, VCA-positive and produced non-transforming EBV, could also be infected by HTLV-III. However, 3 EBV genome- and T4 antigen-negative B-cell lines could only be infected with HTLV-III after successful conversion to an EBV-genome-positive state by pre-infection with EBV. Five other EBV-genome-positive B-cell lines lacking T4 antigens were not infectible with HTLV-III even after super-infection with EBV. Incomplete inhibition of the HTLV-III infection of a T4-positive (LDV-7) and a T4-negative (Craig) was obtained by preadsorption with specific MAb to T4 (OKT4A and Leu 3A). From these observations, it is not clear whether the presence of T4 antigen on the cell surface is needed for the infection of B lymphoblastoid cells; however, successful infection does depend upon the presence of the EBV genome. The mechanism of interaction of HTLV-III and EBV-infected B-cell lines permitting this infection is not fully understood. Although the clinical implications of these observations remain to be determined, it is possible that infection of EBV-positive B-cells may contribute to aberrant humoral responses and/or increased frequency of B-cell malignancies observed in HTLV-III-infected individuals.

Antigens, Differentiation, T-Lymphocyte↗