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Book: HIV interactions with host cell proteins

Spearman, Paul

(Current topics in microbiology and immunology ; 339)

2009

Author's details	Paul Spearman ... ed
Series title	Current topics in microbiology and immunology ; 339
Collection
Keywords	HIV ; Wirtszelle ; Zellproteine ; Wechselwirkung
Subject	Wechselwirkungen ; Interaktion ; Zelleiweiss ; Zelluläre Proteine ; Aids-Virus ; HTLV-III ; LAV/HTLV-III ; HIV-1 ; Human immunodeficiency virus
Language	English
Size	X, 204 S. : Ill., graph. Darst.
Publisher	Springer
Publishing place	Berlin u.a.
Publishing country	Germany
Document type	Book
HBZ-ID	HT016182416
ISBN	978-3-642-02174-9 ; 9783642021756 ; 3-642-02174-3 ; 3642021751
Database	Catalogue ZB MED Medicine, Health

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Shelf mark	Loan status	Location
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Article ; Online: Diagnostic testing for SARS-CoV-2/COVID19.

Spearman, Paul

Current opinion in pediatrics

2020 Volume 33, Issue 1, Page(s) 122–128

Abstract: Purpose of review: SARS-CoV-2 is the novel human coronavirus responsible for the COVID19 pandemic. Accurate detection of infection with SARS-CoV-2 is an essential component of efforts to treat individual patients and to contain spread of the virus in ... ...

Abstract	Purpose of review: SARS-CoV-2 is the novel human coronavirus responsible for the COVID19 pandemic. Accurate detection of infection with SARS-CoV-2 is an essential component of efforts to treat individual patients and to contain spread of the virus in the community. The purpose of this review is to describe current diagnostic modalities for SARS-CoV-2 and outline their use. Special considerations for pediatric age groups are included. Recent findings: RNA PCR from the upper respiratory tract remains the gold standard for detection of infection with SARS-CoV-2. Antigen testing is being widely deployed as a faster and more convenient alternative to PCR, but is less sensitive and should only be used for diagnosis early after symptom onset. Serologic assays can document prior infection and are helpful in diagnosing multisystem inflammatory syndrome in children. Serologic testing should not be used to diagnose acute or active infection. Immune assays are likely to provide a useful measure of protection against COVID19 in the future as knowledge of protective responses improves. Summary: A variety of SARS-CoV-2 diagnostics have recently been developed and deployed. Clinicians should understand the appropriate use and interpretation of RNA PCR, antigen testing and immune assays for SARS-CoV-2 in order to diagnose and treat patients in this evolving pandemic.
MeSH term(s)	COVID-19/diagnosis ; COVID-19 Testing ; Diagnostic Techniques and Procedures ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome
Language	English
Publishing date	2020-12-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1049374-8
ISSN	1531-698X ; 1040-8703
ISSN (online)	1531-698X
ISSN	1040-8703
DOI	10.1097/MOP.0000000000000972
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Article ; Online: Viral and Host Factors Regulating HIV-1 Envelope Protein Trafficking and Particle Incorporation.

Anokhin, Boris / Spearman, Paul

Viruses

2022 Volume 14, Issue 8

Abstract: The HIV-1 envelope glycoprotein (Env) is an essential structural component of the virus, serving as the receptor-binding protein and principal neutralizing determinant. Env trimers are incorporated into developing particles at the plasma membrane of ... ...

Abstract	The HIV-1 envelope glycoprotein (Env) is an essential structural component of the virus, serving as the receptor-binding protein and principal neutralizing determinant. Env trimers are incorporated into developing particles at the plasma membrane of infected cells. Incorporation of HIV-1 Env into particles in T cells and macrophages is regulated by the long Env cytoplasmic tail (CT) and the matrix region of Gag. The CT incorporates motifs that interact with cellular factors involved in endosomal trafficking. Env follows an unusual pathway to arrive at the site of particle assembly, first traversing the secretory pathway to the plasma membrane (PM), then undergoing endocytosis, followed by directed sorting to the site of particle assembly on the PM. Many aspects of Env trafficking remain to be defined, including the sequential events that occur following endocytosis, leading to productive recycling and particle incorporation. This review focuses on the host factors and pathways involved in Env trafficking, and discusses leading models of Env incorporation into particles.
MeSH term(s)	Carrier Proteins/metabolism ; HIV-1/physiology ; Protein Transport ; Virus Assembly ; env Gene Products, Human Immunodeficiency Virus/metabolism ; gag Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	Carrier Proteins ; env Gene Products, Human Immunodeficiency Virus ; gag Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2022-08-05
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081729
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Article: Incorporation of the HIV-1 envelope glycoprotein into viral particles is regulated by the tubular recycling endosome in a cell type-specific manner.

Lerner, Grigoriy / Ding, Lingmei / Candor, Kathleen / Spearman, Paul

bioRxiv : the preprint server for biology

2023

Abstract: The HIV-1 envelope glycoprotein (Env) is incorporated into particles during assembly on the plasma membrane (PM). Env initially reaches the PM through the secretory pathway, after which it is rapidly endocytosed via an AP-2- and clathrin-dependent ... ...

Abstract	The HIV-1 envelope glycoprotein (Env) is incorporated into particles during assembly on the plasma membrane (PM). Env initially reaches the PM through the secretory pathway, after which it is rapidly endocytosed via an AP-2- and clathrin-dependent mechanism. Here we show that endocytosed cell surface Env enters the tubular recycling endosome compartment (TRE). Trafficking to the TRE was dependent upon motifs within the CT previously implicated in Env recycling and particle incorporation. Depletion of TRE components MICAL-L1 or EHD1 led to defects in Env incorporation, particle infectivity, and viral replication. Remarkably, defects were limited to cell types defined as nonpermissive for incorporation of CT-deleted Env, including monocyte-derived macrophages, and not observed in 293T, HeLa, or MT-4 cells. This work identifies the TRE as an essential component of Env trafficking and particle incorporation, and provides evidence that the cell type-dependent incorporation of Env is defined by interactions with components of the TRE.
Language	English
Publishing date	2023-12-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.17.572063
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Article ; Online: Tryptophan-based motifs in the LLP3 region of the HIV-1 envelope glycoprotein cytoplasmic tail direct trafficking to the endosomal recycling compartment and mediate particle incorporation.

Lerner, Grigoriy / Ding, Lingmei / Spearman, Paul

Journal of virology

2023 Volume 97, Issue 10, Page(s) e0063123

Abstract: Importance: The HIV-1 envelope glycoprotein (Env) is an essential component of the virus and has an exceedingly long cytoplasmic tail (CT). Previous studies have suggested that trafficking signals in the CT interact with host factors to regulate the ... ...

Abstract	Importance: The HIV-1 envelope glycoprotein (Env) is an essential component of the virus and has an exceedingly long cytoplasmic tail (CT). Previous studies have suggested that trafficking signals in the CT interact with host factors to regulate the incorporation of Env into particles. One particular area of interest is termed lentiviral lytic peptide 3 (LLP3), as small deletions in this region have been shown to disrupt Env incorporation. In this study, we identify a small region within LLP3 that regulates how Env associates with cellular recycling compartments. Mutants that reduced or eliminated Env from the recycling compartment also reduced Env incorporation into particles. These findings emphasize the importance of two tryptophan motifs in LLP3 for the incorporation of Env into particles and provide additional support for the idea that the CT interacts with host recycling pathways to determine particle incorporation.
MeSH term(s)	Endosomes/metabolism ; env Gene Products, Human Immunodeficiency Virus/chemistry ; env Gene Products, Human Immunodeficiency Virus/metabolism ; Glycoproteins/chemistry ; Glycoproteins/metabolism ; HIV-1/physiology ; Peptides/chemistry ; Peptides/metabolism ; Tryptophan/metabolism ; Cytoplasm/metabolism ; Humans ; Host Microbial Interactions ; Virus Assembly ; Amino Acid Motifs ; Protein Transport
Chemical Substances	env Gene Products, Human Immunodeficiency Virus ; Glycoproteins ; Peptides ; Tryptophan (8DUH1N11BX)
Language	English
Publishing date	2023-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00631-23
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Article: Tryptophan-based motifs in the LLP3 Region of the HIV-1 envelope glycoprotein cytoplasmic tail direct trafficking to the endosomal recycling compartment and mediate particle incorporation.

Lerner, Grigoriy / Ding, Lingmei / Spearman, Paul

bioRxiv : the preprint server for biology

2023

Abstract: The HIV-1 envelope glycoprotein complex (Env) is incorporated into developing particles at the plasma membrane (PM). The cytoplasmic tail (CT) of Env is known to play an essential role in particle incorporation, while the exact mechanisms underlying this ...

Abstract	The HIV-1 envelope glycoprotein complex (Env) is incorporated into developing particles at the plasma membrane (PM). The cytoplasmic tail (CT) of Env is known to play an essential role in particle incorporation, while the exact mechanisms underlying this function of the CT remain uncertain. Upon reaching the PM, trafficking signals in the CT interact with host cell endocytic machinery, directing Env into endosomal compartments within the cell. Prior studies have suggested that Env must traffic through the endosomal recycling compartment (ERC) in order for Env to return to the plasma membrane (PM) site of particle assembly. Expression of a truncated form of the ERC-resident trafficking adaptor Rab11-Family Interacting Proteins C (FIP1C) resulted in CT-dependent sequestration of Env in the condensed ERC, preventing recycling of Env to the PM. In this work, the motifs within the CT responsible for ERC localization of Env were systematically mapped. A small deletion encompassing the N-terminal portion of LLP3 eliminated ERC localization. Site-directed mutagenesis identified two tryptophan-based motifs (WE Importance: The HIV-1 envelope glycoprotein (Env) is an essential component of the virus, and has an exceedingly long cytoplasmic tail (CT). Previous studies have suggested that trafficking signals in the CT interact with host factors to regulate the incorporation of Env into particles. One particular area of interest is termed lentiviral lytic peptide 3 (LLP3), as small deletions in this region have been shown to disrupt Env incorporation. In this study, we identify a small region within LLP3 that regulates how Env associates with cellular recycling compartments. Mutants that reduced or eliminated Env from the recycling compartment also reduced Env incorporation into particles. These findings emphasize the importance of two tryptophan motifs in LLP3 to the incorporation of Env into particles, and provide additional support for the idea that the CT interacts with host recycling pathways to determine particle incorporation.
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.28.538708
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Viral interactions with host cell Rab GTPases.

Spearman, Paul

Small GTPases

2017 Volume 9, Issue 1-2, Page(s) 192–201

Abstract: Viruses are obligate intracellular parasites that utilize cellular machinery for many aspects of their replication cycles. Enveloped viruses generally rely upon host vesicular trafficking machinery to direct their structural proteins and genomes to sites ...

Abstract	Viruses are obligate intracellular parasites that utilize cellular machinery for many aspects of their replication cycles. Enveloped viruses generally rely upon host vesicular trafficking machinery to direct their structural proteins and genomes to sites of virus replication, assembly, and budding. Rab GTPases have been implicated in the replication of many important viral pathogens infecting humans. This review provides a summary of virus-Rab protein interactions, with a particular focus on the role of Rab-related trafficking pathways on late events in the lifecycle of herpesviruses and of HIV-1.
MeSH term(s)	Host-Pathogen Interactions ; Humans ; Virus Physiological Phenomena ; Virus Replication ; Viruses/metabolism ; rab GTP-Binding Proteins/metabolism
Chemical Substances	rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2017-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2682247-7
ISSN	2154-1256 ; 2154-1248
ISSN (online)	2154-1256
ISSN	2154-1248
DOI	10.1080/21541248.2017.1346552
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Article ; Online: Advances in HIV-1 Assembly.

Lerner, Grigoriy / Weaver, Nicholas / Anokhin, Boris / Spearman, Paul

Viruses

2022 Volume 14, Issue 3

Abstract: The assembly of HIV-1 particles is a concerted and dynamic process that takes place on the plasma membrane of infected cells. An abundance of recent discoveries has advanced our understanding of the complex sequence of events leading to HIV-1 particle ... ...

Abstract	The assembly of HIV-1 particles is a concerted and dynamic process that takes place on the plasma membrane of infected cells. An abundance of recent discoveries has advanced our understanding of the complex sequence of events leading to HIV-1 particle assembly, budding, and release. Structural studies have illuminated key features of assembly and maturation, including the dramatic structural transition that occurs between the immature Gag lattice and the formation of the mature viral capsid core. The critical role of inositol hexakisphosphate (IP6) in the assembly of both the immature and mature Gag lattice has been elucidated. The structural basis for selective packaging of genomic RNA into virions has been revealed. This review will provide an overview of the HIV-1 assembly process, with a focus on recent advances in the field, and will point out areas where questions remain that can benefit from future investigation.
MeSH term(s)	HIV-1/genetics ; Virion/metabolism ; Virus Assembly ; gag Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	gag Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2022-02-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14030478
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Article ; Online: HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors.

Spearman, Paul

Current topics in medicinal chemistry

2015 Volume 16, Issue 10, Page(s) 1154–1166

Abstract: HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent the formation and release of infectious particles. Until ... ...

Abstract	HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent the formation and release of infectious particles. Until recently, however, only the catalytic site protease inhibitors have been available to inhibit late stages of HIV replication. This review summarizes the current state of development of antivirals that target Gag or disrupt late events in the retrovirus lifecycle such as maturation of the viral capsid. Maturation inhibitors represent an exciting new series of antiviral compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase inhibitors that inhibit maturation by a completely different mechanism. Numerous small molecules and peptides targeting CA have been studied in attempts to disrupt steps in assembly. Efforts to target CA have recently gained considerable momentum from the development of small molecules that bind CA and alter capsid stability at the post-entry stage of the lifecycle. Efforts to develop antivirals that inhibit incorporation of genomic RNA or to inhibit late budding events remain in preliminary stages of development. Overall, the development of novel antivirals targeting Gag and the late stages in HIV replication appears much closer to success than ever, with the new maturation inhibitors leading the way.
MeSH term(s)	Anti-HIV Agents/chemistry ; Anti-HIV Agents/pharmacology ; Capsid/drug effects ; Capsid/metabolism ; HIV-1/drug effects ; HIV-1/growth & development ; Humans ; Peptides/chemistry ; Peptides/pharmacology ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Virus Replication/drug effects ; gag Gene Products, Human Immunodeficiency Virus/antagonists & inhibitors ; gag Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	Anti-HIV Agents ; Peptides ; Small Molecule Libraries ; gag Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2015-09-04
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2064823-6
ISSN	1873-4294 ; 1568-0266
ISSN (online)	1873-4294
ISSN	1568-0266
DOI	10.2174/1568026615666150902102143
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Article ; Online: HIV-1 Broadly Neutralizing Antibodies Take the Road Less Traveled, and That Makes All the Difference.

Roskin, Krishnan / Spearman, Paul

Cell host & microbe

2020 Volume 27, Issue 4, Page(s) 487–488

Abstract: Broadly neutralizing antibodies (bnAbs) against HIV-1 provide critical insights into co-evolution between the virus and human B cell responses. In this issue of Cell Host & Microbe, Shen et al. (2020) describe a rare mutation in an antibody lineage ... ...

Abstract	Broadly neutralizing antibodies (bnAbs) against HIV-1 provide critical insights into co-evolution between the virus and human B cell responses. In this issue of Cell Host & Microbe, Shen et al. (2020) describe a rare mutation in an antibody lineage targeting the fusion peptide of HIV-1 envelope creating a critical bifurcation, with only one path leading to bnAb development.
MeSH term(s)	Antibodies, Neutralizing/genetics ; Broadly Neutralizing Antibodies ; HIV Antibodies/genetics ; HIV Infections ; HIV-1/immunology ; Humans ; Mutation
Chemical Substances	Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; HIV Antibodies
Language	English
Publishing date	2020-04-14
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2020.03.017
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