Irvin S. Y. Chen

Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates (2007)

An, Dong Sung, Donahue, Robert E., Kamata, Masakazu, Poon, Betty, Metzger, Mark, Mao, Si-Hua, ...

RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions,...

Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5 (2003)

Qin, Xiao-Feng, An, Dong Sung, Chen, Irvin S. Y., Baltimore, David

Double-stranded RNAs approximate to 21 nucleotides long [small interfering RNA (siRNA)] are recognized as powerful reagents to reduce the expression of specific genes. To use them as reagents to...

Maternal HIV-1 viral load and vertical transmission of infection: The Ariel Project for the prevention of HIV transmission from mother to infant (1997)

Cao, Yunzhen, Krogstad, Paul, Korber, Bette T., Koup, Richard A., Muldoon, Mark, Macken, Catherine, ...

Most HIV-1 infections of children result from mother-to-infant transmission, which may occur perinatally or postnatally, as a consequence of breast feeding1−8. In this study, the influence of...

Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells

Stewart, Sheila A., Poon, Betty, Jowett, Jeremy B. M., Xie, Yiming, Chen, Irvin S. Y.

Most current anticancer therapies act by inducing tumor cell stasis followed by apoptosis. HIV-1 Vpr effectively induces apoptosis of T cells after arrest of cells at a G2/M checkpoint. Here, we...

The Presence of Human Immunodeficiency Virus Type 1 Vpr Correlates with a Decrease in the Frequency of Mutations in a Plasmid Shuttle Vector

Jowett, Jeremy B., Xie, Yi-ming, Chen, Irvin S. Y.

The human immunodeficiency virus type 1 (HIV-1) Vpr protein induces cell cycle arrest at the border of G2 and M similar to the arrest caused by agents which damage DNA. We determined whether the...

An Inducible Human Immunodeficiency Virus Type 1 (HIV-1) Vector Which Effectively Suppresses HIV-1 Replication

An, Dong Sung, Morizono, Kouki, Li, Qi-Xiang, Mao, Si Hua, Lu, Stephanie, Chen, Irvin S. Y.

Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which...

Identification of a Domain within the Human T-Cell Leukemia Virus Type 2 Envelope Required for Syncytium Induction and Replication

Poon, Betty, Chen, Irvin S. Y.

In vitro infection by human T-cell leukemia virus type 1 and 2 (HTLV-1 and HTLV-2) can result in syncytium formation, facilitating viral entry. Using cell lines that were susceptible to...

Cryoelectron Microscopic Examination of Human Immunodeficiency Virus Type 1 Virions with Mutations in the Cyclophilin A Binding Loop

Kong, Lawrence B., An, DongSung, Ackerson, Bradley, Canon, Jude, Rey, Osvaldo, Chen, Irvin S. Y., ...

The human immunodeficiency virus type 1 capsid protein contains a conserved P217X4PX2PX5P231 motif. Mutation at Pro-222 decreases virion incorporation of cyclophilin A, while mutation at Pro-231...

Potential Contributions of Viral Envelope and Host Genetic Factors in a Human Immunodeficiency Virus Type 1-Infected Long-Term Survivor

Grovit-Ferbas, Kathie, Ferbas, John, Gudeman, Vaheideh, Sadeghi, Saeed, Goetz, Matthew Bidwell, Giorgi, Janis V., ...

The lack of clinical progression in some individuals despite prolonged human immunodeficiency virus type 1 (HIV-1) infection may result from infection with less-pathogenic viral strains. To address...

Marking and Gene Expression by a Lentivirus Vector in Transplanted Human and Nonhuman Primate CD34+ Cells

An, Dong Sung, Wersto, Robert P., Agricola, Brian A., Metzger, Mark E., Lu, Stephanie, Amado, Rafael G., ...

Recently, gene delivery vectors based on human immunodeficiency virus (HIV) have been developed as an alternative mode of gene delivery. These vectors have a number of advantages, particularly in...

Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation

Stewart, Sheila A., Poon, Betty, Song, Joo Y., Chen, Irvin S. Y.

Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion. Vpr induces cell cycle arrest at the G2/M phase of the cell cycle, and this...

Human Immunodeficiency Virus Type 1 Pathogenesis in SCID-hu Mice Correlates with Syncytium-Inducing Phenotype and Viral Replication

Camerini, David, Su, Hua-Poo, Gamez-Torre, Graciela, Johnson, Michael L., Zack, Jerome A., Chen, Irvin S. Y.

Human immunodeficiency virus type 1 (HIV-1) patient isolates and molecular clones were used to analyze the determinants responsible for human CD4+ thymocyte depletion in SCID-hu mice....

A Murine Leukemia Virus (MuLV) Long Terminal Repeat Derived from Rhesus Macaques in the Context of a Lentivirus Vector and MuLV gag Sequence Results in High-Level Gene Expression in Human T Lymphocytes

Kung, Sam K. P., An, Dong Sung, Chen, Irvin S. Y.

We constructed human immunodeficiency virus type 1 (HIV-1) vectors that will allow higher levels of gene expression in T cells. Gene expression under the control of an internal cytomegalovirus (CMV)...

Human Immunodeficiency Virus Env-Independent Infection of Human CD4− Cells

Pang, Shen, Yu, Duan, An, Dong Sung, Baldwin, Gayle C., Xie, Yiming, Poon, Betty, ...

CD4− epithelial cells covering mucosal surfaces serve as the primary barrier to prevent human immunodeficiency virus type 1 (HIV-1) infection. We used HIV-1 vectors carrying the enhanced green...

Envelope Gene of the Human Endogenous Retrovirus HERV-W Encodes a Functional Retrovirus Envelope

An, Dong Sung, Xie, Yi-ming, Chen, Irvin S. Y.

A member of the human endogenous retrovirus (HERV) family termed HERV-W encodes a highly fusogenic membrane glycoprotein that appears to be expressed specifically in the placenta. It is unclear...

Lentivirus Vector-Mediated Hematopoietic Stem Cell Gene Transfer of Common Gamma-Chain Cytokine Receptor in Rhesus Macaques

An, Dong Sung, Kung, Sam K. P., Bonifacino, Aylin, Wersto, Robert P., Metzger, Mark E., Agricola, Brian A., ...

Nonhuman primate model systems of autologous CD34+ cell transplant are the most effective means to assess the safety and capabilities of lentivirus vectors. Toward this end, we tested the efficiency...

Antibody-Directed Targeting of Retroviral Vectors via Cell Surface Antigens

Morizono, Kouki, Bristol, Gregory, Xie, Yi-ming, Kung, Sam Kam-Pun, Chen, Irvin S. Y.

Targeted stable transduction of specific cells is a highly desirable goal for gene therapy applications. We report an efficient and broadly applicable approach for targeting retroviral vectors to...

A Preponderance of CCR5+ CXCR4+ Mononuclear Cells Enhances Gastrointestinal Mucosal Susceptibility to Human Immunodeficiency Virus Type 1 Infection

Poles, Michael A., Elliott, Julie, Taing, Philip, Anton, Peter A., Chen, Irvin S. Y.

The gastrointestinal mucosa harbors the majority of the body's CD4+ cells and appears to be uniquely susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We undertook this study to...

Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes

Yang, Otto O., Nguyen, Phuong Thi, Kalams, Spyros A., Dorfman, Tanya, Göttlinger, Heinrich G., Stewart, Sheila, ...

Although Nef has been proposed to effect the escape of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTL) through downmodulation of major histocompatibility complex class...

Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5

Qin, Xiao-Feng, An, Dong Sung, Chen, Irvin S. Y., Baltimore, David

Double-stranded RNAs ≈21 nucleotides long [small interfering RNA (siRNA)] are recognized as powerful reagents to reduce the expression of specific genes. To use them as reagents to protect cells...

Depletion of Wee-1 Kinase Is Necessary for both Human Immunodeficiency Virus Type 1 Vpr- and Gamma Irradiation-Induced Apoptosis

Yuan, Huidong, Xie, Yi-Ming, Chen, Irvin S. Y.

Human immunodeficiency virus (HIV) protein R (Vpr) induces G2 arrest, and prolonged G2 arrest leads to apoptosis. We find that in HeLa cells the cell cycle regulatory kinase, Wee-1, is depleted...

Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Enhances Expression from Unintegrated HIV-1 DNA

Poon, Betty, Chen, Irvin S. Y.

Retroviral DNA synthesized prior to integration, termed unintegrated viral DNA, is classically believed to be transcriptionally inert and to serve only as a precursor to the transcriptionally active...

Increased Levels of Wee-1 Kinase in G2 Are Necessary for Vpr- and Gamma Irradiation-Induced G2 Arrest

Yuan, Huidong, Kamata, Masakazu, Xie, Yi-Ming, Chen, Irvin S. Y.

Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle arrest at the G2/M transition and subsequently apoptosis. Here we examined the potential involvement of Wee-1 in Vpr-induced G2...

Lentivirus-delivered stable gene silencing by RNAi in primary cells

STEWART, SHEILA A., DYKXHOORN, DEREK M., PALLISER, DEBORAH, MIZUNO, HANA, YU, EVAN Y., AN, DONG SUNG, ...

Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis...

Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells

Stewart, Sheila A., Poon, Betty, Jowett, Jeremy B. M., Xie, Yiming, Chen, Irvin S. Y.

Most current anticancer therapies act by inducing tumor cell stasis followed by apoptosis. HIV-1 Vpr effectively induces apoptosis of T cells after arrest of cells at a G2/M checkpoint. Here, we...

The Presence of Human Immunodeficiency Virus Type 1 Vpr Correlates with a Decrease in the Frequency of Mutations in a Plasmid Shuttle Vector

Jowett, Jeremy B., Xie, Yi-ming, Chen, Irvin S. Y.

The human immunodeficiency virus type 1 (HIV-1) Vpr protein induces cell cycle arrest at the border of G2 and M similar to the arrest caused by agents which damage DNA. We determined whether the...

An Inducible Human Immunodeficiency Virus Type 1 (HIV-1) Vector Which Effectively Suppresses HIV-1 Replication

An, Dong Sung, Morizono, Kouki, Li, Qi-Xiang, Mao, Si Hua, Lu, Stephanie, Chen, Irvin S. Y.

Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which...

Identification of a Domain within the Human T-Cell Leukemia Virus Type 2 Envelope Required for Syncytium Induction and Replication

Poon, Betty, Chen, Irvin S. Y.

In vitro infection by human T-cell leukemia virus type 1 and 2 (HTLV-1 and HTLV-2) can result in syncytium formation, facilitating viral entry. Using cell lines that were susceptible to...

Cryoelectron Microscopic Examination of Human Immunodeficiency Virus Type 1 Virions with Mutations in the Cyclophilin A Binding Loop

Kong, Lawrence B., An, DongSung, Ackerson, Bradley, Canon, Jude, Rey, Osvaldo, Chen, Irvin S. Y., ...

The human immunodeficiency virus type 1 capsid protein contains a conserved P217X4PX2PX5P231 motif. Mutation at Pro-222 decreases virion incorporation of cyclophilin A, while mutation at Pro-231...

Potential Contributions of Viral Envelope and Host Genetic Factors in a Human Immunodeficiency Virus Type 1-Infected Long-Term Survivor

Grovit-Ferbas, Kathie, Ferbas, John, Gudeman, Vaheideh, Sadeghi, Saeed, Goetz, Matthew Bidwell, Giorgi, Janis V., ...

The lack of clinical progression in some individuals despite prolonged human immunodeficiency virus type 1 (HIV-1) infection may result from infection with less-pathogenic viral strains. To address...

Marking and Gene Expression by a Lentivirus Vector in Transplanted Human and Nonhuman Primate CD34+ Cells

An, Dong Sung, Wersto, Robert P., Agricola, Brian A., Metzger, Mark E., Lu, Stephanie, Amado, Rafael G., ...

Recently, gene delivery vectors based on human immunodeficiency virus (HIV) have been developed as an alternative mode of gene delivery. These vectors have a number of advantages, particularly in...

Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation

Stewart, Sheila A., Poon, Betty, Song, Joo Y., Chen, Irvin S. Y.

Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion. Vpr induces cell cycle arrest at the G2/M phase of the cell cycle, and this...

Human Immunodeficiency Virus Type 1 Pathogenesis in SCID-hu Mice Correlates with Syncytium-Inducing Phenotype and Viral Replication

Camerini, David, Su, Hua-Poo, Gamez-Torre, Graciela, Johnson, Michael L., Zack, Jerome A., Chen, Irvin S. Y.

Human immunodeficiency virus type 1 (HIV-1) patient isolates and molecular clones were used to analyze the determinants responsible for human CD4+ thymocyte depletion in SCID-hu mice....

A Murine Leukemia Virus (MuLV) Long Terminal Repeat Derived from Rhesus Macaques in the Context of a Lentivirus Vector and MuLV gag Sequence Results in High-Level Gene Expression in Human T Lymphocytes

Kung, Sam K. P., An, Dong Sung, Chen, Irvin S. Y.

We constructed human immunodeficiency virus type 1 (HIV-1) vectors that will allow higher levels of gene expression in T cells. Gene expression under the control of an internal cytomegalovirus (CMV)...

Human Immunodeficiency Virus Env-Independent Infection of Human CD4− Cells

Pang, Shen, Yu, Duan, An, Dong Sung, Baldwin, Gayle C., Xie, Yiming, Poon, Betty, ...

CD4− epithelial cells covering mucosal surfaces serve as the primary barrier to prevent human immunodeficiency virus type 1 (HIV-1) infection. We used HIV-1 vectors carrying the enhanced green...

Envelope Gene of the Human Endogenous Retrovirus HERV-W Encodes a Functional Retrovirus Envelope

An, Dong Sung, Xie, Yi-ming, Chen, Irvin S. Y.

A member of the human endogenous retrovirus (HERV) family termed HERV-W encodes a highly fusogenic membrane glycoprotein that appears to be expressed specifically in the placenta. It is unclear...

Lentivirus Vector-Mediated Hematopoietic Stem Cell Gene Transfer of Common Gamma-Chain Cytokine Receptor in Rhesus Macaques

An, Dong Sung, Kung, Sam K. P., Bonifacino, Aylin, Wersto, Robert P., Metzger, Mark E., Agricola, Brian A., ...

Nonhuman primate model systems of autologous CD34+ cell transplant are the most effective means to assess the safety and capabilities of lentivirus vectors. Toward this end, we tested the efficiency...

Antibody-Directed Targeting of Retroviral Vectors via Cell Surface Antigens

Morizono, Kouki, Bristol, Gregory, Xie, Yi-ming, Kung, Sam Kam-Pun, Chen, Irvin S. Y.

Targeted stable transduction of specific cells is a highly desirable goal for gene therapy applications. We report an efficient and broadly applicable approach for targeting retroviral vectors to...

A Preponderance of CCR5+ CXCR4+ Mononuclear Cells Enhances Gastrointestinal Mucosal Susceptibility to Human Immunodeficiency Virus Type 1 Infection

Poles, Michael A., Elliott, Julie, Taing, Philip, Anton, Peter A., Chen, Irvin S. Y.

The gastrointestinal mucosa harbors the majority of the body's CD4+ cells and appears to be uniquely susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We undertook this study to...

Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes

Yang, Otto O., Nguyen, Phuong Thi, Kalams, Spyros A., Dorfman, Tanya, Göttlinger, Heinrich G., Stewart, Sheila, ...

Although Nef has been proposed to effect the escape of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTL) through downmodulation of major histocompatibility complex class...

Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5

Qin, Xiao-Feng, An, Dong Sung, Chen, Irvin S. Y., Baltimore, David

Double-stranded RNAs ≈21 nucleotides long [small interfering RNA (siRNA)] are recognized as powerful reagents to reduce the expression of specific genes. To use them as reagents to protect cells...

Depletion of Wee-1 Kinase Is Necessary for both Human Immunodeficiency Virus Type 1 Vpr- and Gamma Irradiation-Induced Apoptosis

Yuan, Huidong, Xie, Yi-Ming, Chen, Irvin S. Y.

Human immunodeficiency virus (HIV) protein R (Vpr) induces G2 arrest, and prolonged G2 arrest leads to apoptosis. We find that in HeLa cells the cell cycle regulatory kinase, Wee-1, is depleted...

Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Enhances Expression from Unintegrated HIV-1 DNA

Poon, Betty, Chen, Irvin S. Y.

Retroviral DNA synthesized prior to integration, termed unintegrated viral DNA, is classically believed to be transcriptionally inert and to serve only as a precursor to the transcriptionally active...

Increased Levels of Wee-1 Kinase in G2 Are Necessary for Vpr- and Gamma Irradiation-Induced G2 Arrest

Yuan, Huidong, Kamata, Masakazu, Xie, Yi-Ming, Chen, Irvin S. Y.

Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle arrest at the G2/M transition and subsequently apoptosis. Here we examined the potential involvement of Wee-1 in Vpr-induced G2...

Lentivirus-delivered stable gene silencing by RNAi in primary cells

STEWART, SHEILA A., DYKXHOORN, DEREK M., PALLISER, DEBORAH, MIZUNO, HANA, YU, EVAN Y., AN, DONG SUNG, ...

Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis...

Use of a Novel Chimeric Mouse Model with a Functionally Active Human Immune System To Study Human Immunodeficiency Virus Type 1 Infection▿

An, Dong Sung, Poon, Betty, Fang, Raphael Ho Tsong, Weijer, Kees, Blom, Bianca, Spits, Hergen, ...

The goal of this study was to develop a small-animal model to study human immunodeficiency virus type 1 (HIV-1) pathogenesis in blood and primary and secondary lymphoid organs. Rag2−/−γc−/−...

Vpr Is Required for Efficient Nef Expression from Unintegrated Human Immunodeficiency Virus Type 1 DNA▿

Poon, Betty, Chang, Michael A., Chen, Irvin S. Y.

Unintegrated human immunodeficiency virus (HIV) DNA are viral DNA products formed naturally during HIV replication. While the integrated proviral DNA form is transcriptionally active and results in...

Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates

An, Dong Sung, Donahue, Robert E., Kamata, Masakazu, Poon, Betty, Metzger, Mark, Mao, Si-Hua, ...

RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions,...

Human Immunodeficiency Virus Type 1 Vpr Binds to the N Lobe of the Wee1 Kinase Domain and Enhances Kinase Activity for Cdc2▿

Kamata, Masakazu, Watanabe, Nobumoto, Nagaoka, Yoshiko, Chen, Irvin S. Y.

Human immunodeficiency virus type 1 Vpr is a virion-associated accessory protein that has multiple activities within an infected cell. One of the most dramatic effects of Vpr is the induction of cell...