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C Cheng-Mayer

Publications and source records attributed to C Cheng-Mayer.

70 records · Page 4Linked to original sources
PubMed1989

Human immunodeficiency virus (HIV) from experimentally infected chimpanzees: isolation and characterization.

Human immunodeficiency virus-1 (HIV-1) isolates obtained from chimpanzees that had undergone various immunosuppressive treatments were characterized by growth on various primary cells and cell lines as well as by restriction endonuclease analysis. Viruses recovered from animals inoculated with uncloned HIV showed genetic variation from the original inoculum, whereas viruses isolated from an animal infected with a molecular clone of HIV did not. In some cases, virus recovery was possible only after enrichment for CD4+ cells by panning, inoculation with a chimpanzee cytomegalovirus, or a combination of these procedures. These findings indicate a role for viral and host cofactors in the control of virus replication and suggest explanations for the absence of clinical manifestations in HIV-infected chimpanzees.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Simultaneous isolation of HIV-1 and HIV-2 from an AIDS patient.

Two distinct human immunodeficiency viruses, HIV-1SF480 and HIV-2UC2 were isolated simultaneously from the blood of an Ivory Coast patient with AIDS. The HIV subtypes were segregated by their differential ability to infect established human cell lines and by the cell surface expression of type-specific viral antigens. The viruses could be distinguished by both immunoblot and Southern blot analyses. The results indicate that an individual can be infected by both HIV subtypes.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Characterization of a noncytopathic HIV-2 strain with unusual effects on CD4 expression.

A new isolate of the human immunodeficiency virus type 2, designated HIV-2UC1, was recovered from an Ivory Coast patient with normal lymphocyte numbers who died with neurologic symptoms. Like some HIV-1 isolates, HIV-2UC1 grows rapidly to high titers in human peripheral blood lymphocytes and macrophages and has a differential ability to productively infect established human cell lines of lymphocytic and monocytic origin. Moreover, infection with this isolate also appears to involve the CD4 antigen. However, unlike other HIV isolates, HIV-2UC1 does not cause cytopathic effects in susceptible T cells nor does it lead to loss of CD4 antigen expression on the cell surface. These results indicate that HIV-2 may be found in individuals with neurologic symptoms and that the biological characteristics of this heterogeneous subgroup can differ from those typical of HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Biologic features of HIV-1 that correlate with virulence in the host.

Individuals infected with the human immunodeficiency virus type 1 (HIV-1) may be asymptomatic or have AIDS-related complex or the acquired immuno deficiency syndrome (AIDS). Little is known about the factors that influence progression of infection to AIDS. In this study of isolates of HIV-1 obtained at intervals during the infection of four individuals, the development of disease was found to be correlated with the emergence of HIV-1 variants that were more cytopathic in vitro as the disease progressed and that replicated more efficiently in a wide variety of different human cells. The biologic properties of HIV-1 in vitro thus appear to reflect its virulence in the host. Further studies of such sequentially isolated viruses may lead to the identification of viral genes that govern pathogenesis.

AIDS-Related Complex↗
PubMed1988

Distinct biological and serological properties of human immunodeficiency viruses from the brain.

Human immunodeficiency viruses from the brain can be distinguished from peripheral blood isolates by their ability to infect established human cell lines and their sensitivity to serum neutralization. Isolates from the brain and lymph nodes obtained from the same person displayed similar host range tropism and susceptibility to serum neutralization; however, the brain isolate infected macrophages more efficiently. These data suggest that brain isolates may represent a distinct subtype of the human immunodeficiency virus.

Antigen-Antibody Reactions↗
PubMed1988

Detection of human immunodeficiency virus (HIV) in serum and body fluids by sequential competition ELISA.

A micro-ELISA based on competition with the biotin-labeled 25 kDa gag (p25gag) recombinant protein of the human immunodeficiency virus (HIV) was compared to commercial antigen capture ELISAs for the detection of viral antigens in a variety of body fluids including serum, cerebro-spinal fluid (CSF), sputum, saliva, milk, semen, vaginal and bronchial fluids, as well as earwash fluid. Two-thirds (24/30) of these specimens contained IgG and/or IgA antibodies to HIV. The results were correlated with the recovery of infectious HIV in culture. The competition ELISA detected the presence of HIV antigen in 4 out of 8 sera, 5 out of 6 CSF and 6 out of 15 other body fluids that were found to contain infectious virus. Comparatively, 5 of the 8 sera, 3 of the 6 CSF, and 2 of the 15 body fluids tested positive for HIV antigen by capture ELISA. The data suggest that the competition test is more effective than the capture method in detecting antigen in CSF and body secretions, which might be due to the presence of immune complexes. However, both ELISA methods showed similar susceptibility to antibody interference in spiked specimens. The results confirm that antigenemia status can be of value in assessing HIV infection when used in combination with other clinical and laboratory data.

Antibodies, Viral↗
PubMed1988

Identification of human immunodeficiency virus subtypes with distinct patterns of sensitivity to serum neutralization.

The human immunodeficiency virus (HIV) type 1 displays a high degree of genetic variation, especially in the glycoprotein (gp120) domain of the envelope gene. To determine whether this genomic heterogeneity leads to the expression of independent HIV subtypes, 12 sera from HIV type 1 antibody-positive individuals were tested for their ability to neutralize 20 HIV isolates of various origins. Four distinct HIV subtypes with different sensitivity to serum neutralization were identified. These results suggest that a finite number of HIV subtypes exist and that the combined use of selected HIV isolates representing several subtypes may be necessary for the development of an effective vaccine.

HIV↗
PubMed1988

HIV heterogeneity and viral pathogenesis.

HIV research in the past year has elucidated many questions relevant to strategies for treatment and control. For instance, there is a greater understanding of the diversity of HIV isolates as well as the wide range of potential cells sensitive to infection. The search for a safe, effective vaccine now calls for more caution in the light of the discovery of neutralization-resistant variants and antibody-mediated enhancement of infection. Efforts to control HIV must take into account the various mechanisms of virus entry into host cells, and the processes involved in cytopathic effects. Moreover, the role of cells of the mononuclear phagocyte system as reservoirs for HIV particles should be recognized. Together with new information about cytokine induction of HIV, the concept of latent infection of monocytes and macrophages has profound implications for virus persistence and dissemination, especially in the seronegative individual. While many factors about HIV have been uncovered in the past year, several questions remain unanswered and new ones have arisen. For instance, in how many ways does the virus kill in host cell? What causes latency and why does it occur in some but not all hosts? How can virus-filled macrophage vesicles be reached by therapeutic agents or prevented from releasing HIV? What surveillance mechanisms allow some productively infected hosts (cells as well as individuals) to survive beyond expectation? These and other questions should provoke future research on this presently complex and challenging pathogen.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human immunodeficiency virus can productively infect cultured human glial cells.

Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus.

Antigens↗
PubMed1987

Mutational analysis of the human immunodeficiency virus: the orf-B region down-regulates virus replication.

Mutations were made by recombinant DNA techniques in an infectious molecular clone of the human immunodeficiency virus San Francisco isolate 2 (HIVSF2) [formerly the prototype isolate of the acquired immunodeficiency syndrome-associated retrovirus (ARV-2)]. The effect of these changes on the replicative and cytopathologic properties of the virus was studied by transfecting modified virus clones into cultured human cells. Mutations in the gag, pol, env, and tat regions precluded virus replication and cytopathology in lymphoid cells. A mutation in orf-A dramatically reduced but did not abolish virus replication. Mutant viruses with deletions in the orf-B region were highly cytopathic and replicated to approximately 5-fold higher levels than wild-type virus. They also produced approximately 5-fold more viral DNA in infected lymphoid cells than did wild-type virus. Thus, the orf-B region may function to down-regulate virus replication. This mutational analysis of the HIVSF2 genome is a means of assessing genes regulating viral replication and cytopathology.

Cloning, Molecular↗
PubMed1987

Patterns of antibody response in individuals infected with the human immunodeficiency virus.

Immunofluorescence and immunoblot assays were conducted on 488 sera from patients with AIDS and clinically healthy individuals at risk for infection by the human immunodeficiency virus. Of these, 360 contained antiviral antibodies, and nearly all reacted with the envelope precursor glycoprotein gp160. Sera from 103 individuals for whom a complete clinical history was available were evaluated in detail. Most sera recognized both the gp160 and the p55 gag precursor protein. Because these two antigens are found primarily in infected cells, the results suggest that this association makes them more immunogenic. A high prevalence of antibodies to the polymerase gene products (p65 and p31) and to a viral protein p48, which is not yet fully defined, was also noted. Many sera, particularly those from patients with Kaposi's sarcoma or Pneumocystis carinii pneumonia, lacked antibodies to both p25 and gp41. These antibody patterns could help predict the prognosis for virus-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Human retroviral env and gag polypeptides: serologic assays to measure infection.

Humoral antiviral responses to human retrovirus infections identify persistently infected individuals and can be used to characterize virus-host interactions. Antibodies to native viral polypeptides have been reliably measured, although quantitation of env antibodies is difficult due to a lack of purified antigens. To quantitate antibodies to env antigens, bacterially expressed cloned env polypeptides from the transmembrane regions of human T lymphotropic virus types I and III were applied to nitrocellulose filters in an immunodot assay. A combination of the sensitivity of the Western blot procedure and the specificity of peptides from defined viral sequences was used to detect 49/49 HTLV-III/LAV-infected individuals previously defined as seropositive by radioimmunoprecipitation sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Of these HTLV-III/LAV envelope seropositive people, 22% lacked antibody to p24 in a radioimmunoassay. In contrast, the sensitivity of antibody detection to HTLV-I env antigens and p24 were comparable. Antibodies to HTLV-I and HTLV-III/LAV env transmembrane peptides were not cross-reactive. Levels of antibody to env antigens of both HTLV-I and HTLV-III/LAV persisted without change for at least 26 mo, suggesting that most infections represent stable virus-host interactions. The use of bacterially expressed env peptides offers a rapid serologic approach for distinguishing human retroviral infections and can be used to define immune responses to specific regions of the viral genome.

Acquired Immunodeficiency Syndrome↗
PubMed1986

AIDS retrovirus (ARV-2) clone replicates in transfected human and animal fibroblasts.

A molecular clone of the AIDS-associated retrovirus (ARV-2) was transfected into human T lymphocyte and monocyte cell lines as well as mouse, mink, monkey, and human fibroblast lines. A replicating virus with cytopathic and biologic properties of ARV-2 was recovered from all the cell lines. The animal and human fibroblast cells are resistant to direct infection by ARV, and in these experiments virus production in the fibroblast lines, especially mouse, was reduced compared to human lymphocytes. However, human fibroblasts were more permissive to virus expression than mouse cells. These results show that, whereas the primary block to ARV infection in certain cells may occur at the cell surface, intracellular mechanisms can also participate in controlling virus replication. The results have relevance to vaccine development and encourage further work with modified molecular clones to examine regions of the ARV genome necessary for cytopathology and replication.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

In vitro infection of primate PBMC with simian/human immunodeficiency virus, SHIV(SF33A): correlation to in vivo outcome.

The macaque/SIV animal system is an important model for studying AIDS pathogenesis and for evaluating the efficacy of vaccines and anti-viral therapeutics. However, differences between HIV-1 and SIV envelope proteins exist that render the SIV/macaque model of limited value when examining envelope determinants of retroviral pathogenesis. To overcome this problem, we utilized a chimeric virus, SHIV(SF33), containing the env gene from HIV-1SF33 in the context of the molecular clone SIVmac239, in the macaque animal model. In this study SHIV(SF33A), a pathogenic virus that evolved in vivo from a rhesus macaque infected intravenously with the molecular clone SHIV(SF33) was used in both in vitro and in vivo studies. By using a cell culture system, we examined the biological properties of our parental and animal-adapted chimeric viruses and compared in vitro susceptibility to in vivo studies.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

In vivo adaptation of SHIV(SF162): chimeric virus expressing a NSI, CCR5-specific envelope protein.

The chemokine receptor CCR5 is known to be a critical determinant of human immunodeficiency virus (HIV) transmission and pathogenesis in the human host. Towards the development of a macaque model to evaluate the efficacy of vaccines and therapeutics against infection with CCR5-specific viruses, and to delineate the pathogenic properties of such viruses, we constructed a chimeric simian human immunodeficiency virus, SHIV(SF162), containing the env, tat, rev, and vpu genes from HIV-1(SF162) (R5, MT/NSI) in the context of the molecular clone simian immunodeficiency virus, SIV(mac239). Virus generated from this molecular clone was used to intravenously infect two juvenile macaques, followed by three consecutive serial blood/bone marrow transfusions. Animals infected with parental SHIV(SF162) (P1) had detectable levels of viral replication (as determined by p27(gag) production) within days of infection; however, viral set-points fell below detection by Week 3. Late passage animals (P3 and P4) had a two-log increase in the level of plasma p27(gag) antigen. These results demonstrate that in vivo serial passage of the R5-specific SHIV(SF162) enhanced its replicative capacity.

AIDS Vaccines↗