Envelope sequences of two new United States HIV-1 isolates

Gurgo, Corrado; Guo, Hongyu; Franchini, Genoveffa; Aldovini, Anna; Collalti, Enrico; Farrell, Karen B.; Wong‐Staal, Flossie; Gallo, Robert C.; Reitz, Marvin S.

doi:10.1016/0042-6822(88)90568-5

Cited by 126 publications

(59 citation statements)

References 19 publications

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“…The conservation of cysteine residues implies that they may be important for some aspect of virus infection and replication apart from cell fusion activity. Nevertheless, a few virus is-olates have been identified that do not maintain this con- served cysteine residue (34)(35)(36)(37). Some of these viruses were isolated from the central nervous system (34)(35)(36) and belong to a unique group of virus isolates which are less effective in down-regulating the surface expression of CD4 in infected cells (38).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a few virus is-olates have been identified that do not maintain this con- served cysteine residue (34)(35)(36)(37). Some of these viruses were isolated from the central nervous system (34)(35)(36) and belong to a unique group of virus isolates which are less effective in down-regulating the surface expression of CD4 in infected cells (38). Interestingly, a recent study with a2A-adrenergic receptors reported that palmitoylation of the cytoplasmic tail is important in mediating down-regulation of the receptor by prolonged agonist exposure (18).…”

Section: Discussionmentioning

confidence: 99%

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The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.

Yang

Spies

Compans

1995

Proc. Natl. Acad. Sci. U.S.A.

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The envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) were found to be modified by fatty acylation of the transmembrane protein subunit gp4l. The precursor gpl60 was also palmitoylated prior to its cleavage into the gpl20 and gp4l subunits. The palmitic acid label was sensitive to treatment with hydroxylamine or 2-mercaptoethanol, indicating that the linkage is through a thioester bond. Treatment with cycloheximide did not prevent the incorporation of [3H]palmitic acid into the HIV envelope protein, indicating that palmitoylation is a posttranslation modification. In contrast to other glycoproteins, which are palmitoylated at cysteine residues within or close to the membrane-spanning hydrophobic domain, the palmitoylation of the HIV-1 envelope proteins occurs on two cysteine residues, Cys-764 and Cys-837, which are 59 and 132 amino acids, respectively, from the proposed membrane-spanning domain of gp4l. Sequence comparison revealed that one of these residues (Cys-764) is conserved in the cytoplasmic domains of almost all HIV-1 isolates and is located very close to an amphipathic region which has been postulated to bind to the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.

Yang

Spies

Compans

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…The sequences were identified and analyzed by the Navigator and Factura DNA analysis software package (Perkin-Elmer). The results were compared to the sequences of the prototypic strains Ba-L, MN, and 89.6, with known macrophage-tropic, T-cell-tropic, and dually tropic phenotypes, respectively (6,16,17).…”

Section: In 1995 Cocchi Et Al Reported Potent In Vitro Human Immunomentioning

confidence: 99%

Combination of CCR5 and CXCR4 Inhibitors in Therapy of Human Immunodeficiency Virus Type 1 Infection: In Vitro Studies of Mixed Virus Infections

Rusconi

Catamancio

Citterio

et al. 2000

J Virol

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We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stromaderived factor 1␤ (SDF-1␤), Met-SDF-1␤, and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas Met-SDF-1␤ had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation.In 1995, Cocchi et al. reported potent in vitro human immunodeficiency virus type 1 (HIV-1) inhibition by three chemokines secreted by CD8 ϩ T lymphocytes (4) and focused attention on this class of molecules with low molecular masses (8 to 12 kDa). The chemokines described, RANTES, macrophage inflammatory protein-1␣ (MIP-1␣), and MIP-1␤, belong to the group of C-C chemokines that block HIV-1 entry into cells (5).Relationships among membrane coreceptors, chemokines, and cellular tropism were further defined in 1996 by Feng et al., who described a novel molecule which acted as a cofactor for T-cell-tropic HIV-1 isolates but not for macrophage-tropic isolates (14). This receptor, which was already known but did not have an identified natural ligand, belongs to the C-X-C chemokine receptor superfamily and was named "fusin," or CXCR4. The receptor for HIV-1 macrophage-tropic isolates was subsequently identified and named C-C chemokine receptor 5 (CCR5). CCR5 reacts with the chemokines RANTES, MIP-1␣, and MIP-1␤ (9, 12). The natural ligand for CXCR4 is stroma derived factor-1 (SDF-1), an ␣-chemokine with chemotactic properties for T lymphocytes and a developmental role in B lymphocyte maturation (2,25).During the early phases of HIV-1 infection, R5 viral strains usually predominate, whereas X4 strains frequently emerge in the late stages of HIV-1 infection, accompanied by a decline in peripheral blood CD4 lymphocytes and a clinical progression toward AIDS (7,34). Viral isolates with a dual tropism could represent a transition phase between viral R5 and X4 phenotypes, or they may represent X4 viruses that have maintained an ability to infect macrophages (31, 33).The aim of our study was to evaluate the interactions between attachment and entry inhibitors of HIV-1 infection. Our experiments suggest that the use of combined inhibitors of R5 and X4 viruses may be useful in inhibiting mixed infections. Analysis of cellular tropism of the different viral isolates on transformed cell lines. The two viral isolates examined in this study, RM and DK, were derived from two patients with primary HIV-1 infection acute syndrome (29), and the isolates were used to infect U87MG-transformed CD4 ϩ cells transfected with CCR5 or CXCR4 coreceptors (8), provided by Dan R. Littman (The Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New Yo...

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“…Envelope genes from the primary MN strain (MN-P) and the TCLA MN strain (MN-TCLA) have been described previously (12,14,22,45). Additional mutant envelope genes were constructed to contain specific segments or sequences of each of the parental genes.…”

Section: Mabsmentioning

confidence: 99%

“…The original isolate of the MN virus was propagated in a continuous T-cell line and is considered T-cell line adapted (TCLA) (12,30). It is unusual among both primary and TCLA strains of HIV-1 in its high sensitivity to neutralization by antibodies in sera of infected patients and monoclonal antibodies (MAbs) against multiple linear and conformation-sensitive epitopes on the envelope glycoproteins (4,7,40,48).…”

mentioning

confidence: 99%

Multiple Interactions across the Surface of the gp120 Core Structure Determine the Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1

Bouma

Leavitt

Zhang

et al. 2003

J Virol

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Resistance to neutralization is an important characteristic of primary isolates of human immunodeficiency virus type 1 (HIV-1) that relates to the potential for successful vaccination to prevent infection and use of immunotherapeutics for treatment of established infection. In order to further elucidate mechanisms responsible for neutralization resistance, we studied the molecular mechanisms that determine the resistance of the primary virus isolate of the strain HIV-1 MN to neutralization by soluble CD4 (sCD4). As is the case for the global neutralization resistance phenotype, sCD4 resistance depended upon sequences in the amino-terminal heptad repeat region of gp41 (HR1), as well as on multiple functional interactions within the envelope complex. The functional interactions that determined the resistance included interactions between the variable loop 1 and 2 (V1/V2) region and sequences in or near the CD4 binding site (CD4bs) and with the V3 loop. Additionally, the V3 loop region was found to interact functionally with sequences in the outer domain of gp120, distant from the CD4bs and coreceptor-binding site, as well as with a residue thought to be located centrally in the coreceptor-binding site. These and previous results provide the basis for a model by which functional signals that determine the neutralization resistance, high-infectivity phenotype depend upon interactions occurring across the surface of the gp120 core structure and involving variable loop structures and gp41. This model should be useful in efforts to define epitopes that may be important for primary virus neutralization.Resistance to antibody-mediated neutralization of infectivity is characteristic of naturally occurring strains of human immunodeficiency virus type 1 (HIV-1) that have not been manipulated in the laboratory (15, 18). Such strains are commonly referred to as primary isolates. This property is a limiting factor with respect to efforts to develop a vaccine that may protect by induction of potent neutralizing antibodies. Induction of potent neutralizing antibodies is a common property of successful viral vaccines (26). Insights into the mechanisms of neutralization resistance of primary isolates of HIV-1 may indicate possible approaches to neutralization of such viruses and facilitate vaccine development.Our laboratory has previously reported studies of the MN strain of HIV-1 that have begun to address this issue (14,(21)(22)(23). The original isolate of the MN virus was propagated in a continuous T-cell line and is considered T-cell line adapted (TCLA) (12, 30). It is unusual among both primary and TCLA strains of HIV-1 in its high sensitivity to neutralization by antibodies in sera of infected patients and monoclonal antibodies (MAbs) against multiple linear and conformation-sensitive epitopes on the envelope glycoproteins (4,7,40,48). In an early study a neutralization-resistant variant of this strain was studied that was produced by growth of the MN strain virus in the presence of a highly neutralizing human serum (22). T...

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Envelope sequences of two new United States HIV-1 isolates

Cited by 126 publications

References 19 publications

The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.

The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.

Combination of CCR5 and CXCR4 Inhibitors in Therapy of Human Immunodeficiency Virus Type 1 Infection: In Vitro Studies of Mixed Virus Infections

Multiple Interactions across the Surface of the gp120 Core Structure Determine the Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1

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