Annexin 2: a Novel Human Immunodeficiency Virus Type 1 Gag Binding Protein Involved in Replication in Monocyte-Derived Macrophages

Ryzhova, Elena; Vos, Robin M.; Albright, Andrew; Harrist, Alexia; Harvey, Thomas S.; González‐Scarano, Francisco

doi:10.1128/jvi.80.6.2694-2704.2006

Cited by 87 publications

(101 citation statements)

References 48 publications

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“…ANXA2 is a multifunctional protein and is involved in many cellular processes, such as fibrinolysis, exocytosis, endocytosis, cell-cell adhesion, and cell motility (36,37,48). ANXA2 has been linked to the life cycle of other positive-sense single-stranded RNA viruses, such as hepatitis C virus (49)(50)(51) and HIV (52)(53)(54). In both cases, a viral protein has been reported to interact with ANXA2 in infected cells, and silencing of ANXA2 affected the infectivity of the viruses.…”

Section: Discussionmentioning

confidence: 99%

The Feline Calicivirus Leader of the Capsid Protein Is Associated with Cytopathic Effect

Abente

Sosnovtsev

Sandoval-Jaime

et al. 2013

J Virol

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Open reading frame 2 (ORF2) of the feline calicivirus (FCV) genome encodes a capsid precursor that is posttranslationally processed to release the mature capsid protein (VP1) and a small protein of 124 amino acids, designated the leader of the capsid (LC). To investigate the role of the LC protein in the virus life cycle, mutations and deletions were introduced into the LC coding region of an infectious FCV cDNA clone. Three cysteine residues that are conserved among all vesivirus LC sequences were found to be critical for the recovery of FCV with a characteristic cytopathic effect in feline kidney cells. A cell-rounding phenotype associated with the transient expression of wild-type and mutagenized forms of the LC correlated with the cytopathic and growth properties of the corresponding engineered viruses. The host cellular protein annexin A2 was identified as a binding partner of the LC protein, consistent with a role for the LC in mediating host cell interactions that alter the integrity of the cell and enable virus spread.M embers of the family Caliciviridae are small nonenveloped viruses that contain a positive-sense single-stranded RNA genome. Feline calicivirus (FCV) is in the genus Vesivirus of the family and has been an important model for studying calicivirus replication because it grows efficiently in cell culture and has a reverse genetics system (1-5). The RNA genomes of caliciviruses range in size from ϳ6.7 to 8.5 kb and typically encode 8 or 9 viral proteins from two (Sapovirus, Nebovirus, and Lagovirus) or three (Norovirus and Vesivirus) open reading frames (ORFs). A unique ORF4 in the murine norovirus genome that encodes a protein reported to downregulate the innate immune response has been identified (6). The 5= end of the viral RNA genome is covalently linked to a VPg protein; the 3= end of the genome is polyadenylated (2, 7-9). The infectious virion is composed of 180 copies of the major capsid protein VP1 and 1 to 10 copies of the minor structural protein VP2, which together form a capsid around the VPg-linked genome (10-15). The genomic RNA serves as a template for translation of the ORF1 polyprotein that is proteolytically cleaved by the viral protease to release the nonstructural proteins (16,17), and an ϳ2.2-to 2.6-kb subgenomic bicistronic RNA template is used for the translation of VP1 and VP2 (7, 18). A genetic feature unique to members of the genus Vesivirus is expression of the major capsid protein from ORF2 as a precursor protein (5,(18)(19)(20). This precursor is processed in trans by the viral protease to release two proteins: the leader of the capsid (LC) and the mature capsid protein (VP1) (5,19,21,22). The function of the LC protein is not clear, but cleavage of the precursor to release LC and VP1 is essential for the recovery of infectious virions (5). Transient expression of the LC was reported to enhance replication of a human norovirus RNA replicon (23), and an increase in the level of mRNA for the low-density lipoprotein receptor (LDLR) was observed (24). We showed previo...

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Section: Discussionmentioning

confidence: 99%

The Feline Calicivirus Leader of the Capsid Protein Is Associated with Cytopathic Effect

Abente

Sosnovtsev

Sandoval-Jaime

et al. 2013

J Virol

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“…Thus Env and Gag must contain appropriate trafficking signals to allow infectious particle assembly in distinct locations. Although some knowledge of intracellular Gag trafficking has been gained (Perlman and Resh, 2006;Ryzhova et al, 2006), little is known about Env targeting in infected cells.…”

Section: Discussionmentioning

confidence: 99%

A Conserved Dileucine Motif Mediates Clathrin and AP-2–dependent Endocytosis of the HIV-1 Envelope Protein

Byland

Vance

Hoxie

et al. 2007

MBoC

124

133

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During the assembly of enveloped viruses viral and cellular components essential for infectious particles must colocalize at specific membrane locations. For the human and simian immunodeficiency viruses (HIV and SIV), sorting of the viral envelope proteins (Env) to assembly sites is directed by trafficking signals located in the cytoplasmic domain of the transmembrane protein gp41 (TM). A membrane proximal conserved GYxxØ motif mediates endocytosis through interaction with the clathrin adaptor AP-2. However, experiments with SIV mac239 Env indicate the presence of additional signals. Here we show that a conserved C-terminal dileucine in HIV HxB2 also mediates endocytosis. Biochemical and morphological assays demonstrate that the C-terminal dileucine motif mediates internalization as efficiently as the GYxxØ motif and that both must be removed to prevent Env internalization. RNAi experiments show that depletion of the clathrin adaptor AP-2 leads to increased plasma membrane expression of HIV Env and that this adaptor is required for efficient internalization mediated by both signals. The redundancy of conserved endocytosis signals and the role of the SIV mac239 Env GYxxØ motif in SIV pathogenesis, suggest that these motifs have functions in addition to endocytosis, possibly related to Env delivery to the site of viral assembly and/or incorporation into budding virions. INTRODUCTIONThe assembly of enveloped animal viruses requires that the viral and cellular components needed to make infectious particles are brought to the same site within the infected cell at the same time. For the primate lentiviruses (the human immunodeficiency viruses types 1 and 2 [HIV-1 and -2] and the simian immunodeficiency viruses [SIV]) the key viral structural proteins required to generate infectious particles are Gag, Gag-Pol, and Env. Although Gag alone can promote the formation of virus-like particles, Env and Gag-Pol are both essential for the formation of infectious virions. Although a considerable amount is known about these proteins, little is understood of the mechanisms through which they are targeted to the sites of assembly in infected cells.In many cell types, HIV assembles at the plasma membrane and, in the course of Gag assembly, the particles derive their membrane from the plasma membrane. For these particles to be infectious, Env must be transported to the cell surface, but the level to which it is incorporated into budding virions is unclear. Recent data have suggested that fewer than 10 Env protein complexes (trimers) are incorporated per virion (Chertova et al., 2002;Zhu et al., 2003), and early studies of HIV infected T-cells showed that much of the newly synthesized Env is transported to lysosomes and degraded (Willey et al., 1988). However, it has recently become evident that in macrophages the assembly of Envcontaining infectious HIV occurs on intracellular membranes, that have some characteristics in common with late endosomes (Raposo et al., 2002;Pelchen-Matthews et al., 2003). The assembly of virus in distinct...

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“…AnxA2 is an interaction partner for HIV-1 Gag in productively infected macrophages, with the interaction most likely taking place at the limiting membrane of endolysosomes. Depletion of AnxA2 led to incomplete Gag processing and reduced infectivity of released virions, suggesting a role for AnxA2 in HIV-1 assembly (Ryzhova et al, 2006). Supporting this, AnxA2/S100A10 complex was present in highly purified virions (Chertova et al, 2006).…”

Section: Intracellular Interactions With Microbesmentioning

confidence: 53%

Emerging functions as host cell factors – an encyclopedia of annexin-pathogen interactions

Kuehnl

Musiol

Raabe

et al. 2016

Biological Chemistry

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Abstract:Emerging infectious diseases and drug-resistant infectious agents call for the development of innovative antimicrobial strategies. With pathogenicity now considered to arise from the complex and bi-directional interplay between a microbe and the host, host cell factor targeting has emerged as a promising approach that might overcome the limitations of classical antimicrobial drug development and could open up novel and efficient therapeutic strategies. Interaction with and modulation of host cell membranes is a recurrent theme in the host-microbe relationship. In this review, we provide an overview of what is currently known about the role of the Ca 2+ dependent, membrane-binding annexin protein family in pathogenhost interactions, and discuss their emerging functions as host cell derived auxiliary proteins in microbe-host interactions and host cell targets.

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Annexin 2: a Novel Human Immunodeficiency Virus Type 1 Gag Binding Protein Involved in Replication in Monocyte-Derived Macrophages

Cited by 87 publications

References 48 publications

The Feline Calicivirus Leader of the Capsid Protein Is Associated with Cytopathic Effect

The Feline Calicivirus Leader of the Capsid Protein Is Associated with Cytopathic Effect

A Conserved Dileucine Motif Mediates Clathrin and AP-2–dependent Endocytosis of the HIV-1 Envelope Protein

Emerging functions as host cell factors – an encyclopedia of annexin-pathogen interactions

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