scholarly journals TRIM22: A Diverse and Dynamic Antiviral Protein

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Clayton J. Hattlmann ◽  
Jenna N. Kelly ◽  
Stephen D. Barr
Keyword(s):  
Evolutionary History ◽  
Encephalomyocarditis Virus ◽  
Antiviral Protein ◽  
Gene Expansion ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Differentiation And Proliferation ◽  
And Function ◽  
Hiv 1

The tripartite motif (TRIM) family of proteins is an evolutionarily ancient group of proteins with homologues identified in both invertebrate and vertebrate species. Human TRIM22 is one such protein that has a dynamic evolutionary history that includes gene expansion, gene loss, and strong signatures of positive selection. To date, TRIM22 has been shown to restrict the replication of a number of viruses, including encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), and human immunodeficiency virus type 1 (HIV-1). In addition, TRIM22 has also been implicated in cellular differentiation and proliferation and may play a role in certain cancers and autoimmune diseases. This comprehensive paper summarizes our current understanding of TRIM22 structure and function.

scholarly journals Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function

2019 ◽  
Vol 93 (12) ◽  
Author(s):  
Hanh T. Nguyen ◽  
Nirmin Alsahafi ◽  
Andrés Finzi ◽  
Joseph G. Sodroski
Keyword(s):  
Envelope Glycoprotein ◽  
Disulfide Bonds ◽  
Virus Entry ◽  
Envelope Proteins ◽  
Immunodeficiency Virus ◽  
Membrane Envelope ◽  
And Function ◽  
State 1 ◽  
Hiv 1

ABSTRACTMost broadly neutralizing antibodies and many entry inhibitors target the pretriggered (state 1) conformation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). Here we examine two previously reported Env mutants designed to be stabilized in this conformation by the introduction of artificial disulfide bonds: A501C/T605C (called SOS) and I201C/A433C (called DS). SOS Env supported virus entry and cell-cell fusion only after exposure to a reducing agent, dithiothreitol (DTT). Deletion of the Env cytoplasmic tail improved the efficiency with which the SOS Env supported virus infection in a reducing environment. The antigenicity of the SOS Env was similar to that of the unmodified Env, except for greater sensitivity to some state 1-preferring ligands. In contrast, viruses with the DS Env were not infectious, even after DTT treatment. The proteolytic maturation of the DS Env on both cell surfaces and virions was severely compromised compared with that of the unmodified Env. The DS Env exhibited detectable cell-fusing activity when DTT was present. However, the profiles of cell-surface Env recognition and cell-cell fusion inhibition by antibodies differed for the DS Env and the unmodified Env. Thus, the DS Env appears to be stabilized in an off-pathway conformation that is nonfunctional on the virus. The SOS change exerted more subtle, context-dependent effects on Env conformation and function.IMPORTANCEThe human immunodeficiency virus type 1 (HIV-1) envelope proteins (Envs) bind receptors on the host cell and change shape to allow the virus to enter the cell. Most virus-inhibiting antibodies and drugs recognize a particular shape of Env called state 1. Disulfide bonds formed by cysteine residues have been introduced into soluble forms of the flexible envelope proteins in an attempt to lock them into state 1 for use in vaccines and as research tools. We evaluated the effect of these cysteine substitutions on the ability of the membrane Env to support virus entry and on susceptibility to inhibition by antibodies and small molecules. We found that the conformation of the envelope proteins with the cysteine substitutions differed from that of the unmodified membrane envelope proteins. Awareness of these effects can assist efforts to create stable HIV-1 Env complexes that more closely resemble the state 1 conformation.

scholarly journals Ineffectual Targeting of HIV-1 Nef by Cytotoxic T Lymphocytes in Acute Infection Results in No Functional Impairment or Viremia Reduction

2014 ◽  
Vol 88 (14) ◽  
pp. 7881-7892 ◽  
Author(s):  
Justin De La Cruz ◽  
Thomas Vollbrecht ◽  
Patricia Frohnen ◽  
Hwee L. Ng ◽  
Eric S. Daar ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Receptor Gene ◽  
Acute Infection ◽  
Cell Receptor ◽  
Immunodeficiency Virus ◽  
Successful Control ◽  
And Function ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACTThe human immunodeficiency virus type 1 (HIV-1) accessory protein Nef is heavily targeted by CD8+T lymphocytes (CTLs) during acute infection and therefore is included in many candidate vaccines. We investigated whether CTL targeting of Nef during acute infection contributes to immune control by disrupting the function of Nef. The sequence and function of Nef in parallel with CTL responses were assessed longitudinally from peak viremia until the viremia set point in a cohort of six subjects with acute infection. All but one individual had a single founder strain. Nef-specific CTL responses were detected in all subjects and declined in magnitude over time. These responses were associated with mutations, but none of the mutations were detected in important functional motifs. Nef-mediated downregulation of CD4 and major histocompatibility complex (MHC) class I molecules was better preserved in acute infection than in chronic infection. Finally, Nef-specific CTL responses were not associated with a reduction in viremia from its acute-phase peak. Our results indicate that CTLs targeting Nef epitopes outside critical functional domains have little effect on the pathogenic functions of Nef, rendering these responses ineffective in acute infection.IMPORTANCEThese data indicate that using the whole Nef protein as a vaccine immunogen likely allows immunodominance that leads to targeting of CTL responses that are rapidly escaped with little effect on Nef-mediated pathogenic functions. Pursuing vaccination approaches that can more precisely direct responses to vulnerable areas would maximize efficacy. Until vaccine-induced targeting can be optimized, other approaches, such as the use of Nef function inhibitors or the pursuit of immunotherapies such as T cell receptor gene therapy or adoptive transfer, may be more likely to result in successful control of viremia.

scholarly journals Dissection of the HIV Vif Interaction with Human E3 Ubiquitin Ligase

2010 ◽  
Vol 84 (14) ◽  
pp. 7135-7139 ◽  
Author(s):  
Leslie S. Wolfe ◽  
Bradford J. Stanley ◽  
Chang Liu ◽  
William K. Eliason ◽  
Yong Xiong
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Titration Calorimetry ◽  
Antiviral Protein ◽  
Immunodeficiency Virus ◽  
Cullin 5 ◽  
Multiple Regions ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) protein Vif recruits the host E3 ubiquitin ligase, composed of cullin 5 (Cul5), Rbx2, Elongin B, and Elongin C (EloBC), to polyubiquitinate the antiviral protein APOBEC3G. Multiple regions in the C-terminal half of Vif interact with the E3 ligase. We have purified individual regions of Vif and investigated their thermodynamic contributions to the ligase assembly in vitro using isothermal titration calorimetry and fluorescence anisotropy. Our results quantify the high-affinity interactions between the Vif BC box and EloBC and between the Vif zinc finger and Cul5, as well as the modest interaction between the Vif cullin box and Cul5. Our purified Vif constructs also provide direct biochemical evidence that the Vif cullin box, containing the PPLP region, leads to the dimerization of Vif-EloBC complexes but not Cul5-Vif-EloBC complexes.

scholarly journals Impaired Quality of the Hepatitis B Virus (HBV)-Specific T-Cell Response in Human Immunodeficiency Virus Type 1-HBV Coinfection

2009 ◽  
Vol 83 (15) ◽  
pp. 7649-7658 ◽  
Author(s):  
J. Judy Chang ◽  
Sunee Sirivichayakul ◽  
Anchalee Avihingsanon ◽  
Alex J. V. Thompson ◽  
Peter Revill ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Responses ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Hepatits B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+ T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+ T-cell count (P = 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+ T-cell count.

scholarly journals Simultaneous Detection of Multiplex-Amplified Human Immunodeficiency Virus Type 1 RNA, Hepatitis C Virus RNA, and Hepatitis B Virus DNA Using a Flow Cytometer Microsphere-Based Hybridization Assay

2000 ◽  
Vol 38 (3) ◽  
pp. 1066-1071 ◽  
Author(s):  
J.-P. Defoort ◽  
M. Martin ◽  
B. Casano ◽  
S. Prato ◽  
C. Camilla ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Flow Cytometer ◽  
Rt Pcr ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Pcr Products ◽  
Hiv 1

The feasibility of performing a multiplex assay for the detection of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNAs and hepatitis B virus (HBV) DNA is demonstrated. This assay is based (i) on the coamplification of a 142-bp fragment from thegag region of the HIV-1 genome and a 142-bp HIV-1 quantitation standard fragment, a 244-bp fragment from the 5′ noncoding region of the HCV genome, and a 104-bp fragment from the pre-C and C gene regions of the HBV genome, using three sets of specific primers; (ii) on the capacity of these four biotinylated PCR products to hybridize to their specific oligonucleotide probe-coated microspheres; and (iii) on the ability of the flow cytometer to discriminate between distinct fluorescent-microsphere categories. Absence of cross-hybridization between the unrelated oligonucleotide probes and PCR products generated by the multiplex reverse transcription-PCR (RT-PCR) and the highly sensitive detection method allowed us to assess unambiguously the HIV-1 viral load and the infectious status of 35 serologically well-established clinical samples and 20 seronegative blood donor plasma samples tested. The results indicate that multiplex RT-PCR and flow cytometer microsphere-based hybridization assays, when combined, provide a rapid, sensitive, and specific method for the quantitation and detection of the major viral agents of infectious diseases in a single plasma sample.

A Synthetic Peptide Derived From Human Immunodeficiency Virus Type 1 gp120 Downregulates the Expression and Function of Chemokine Receptors CCR5 and CXCR4 in Monocytes by Activating the 7-Transmembrane G-Protein–Coupled Receptor FPRL1/LXA4R

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1165-1173
Author(s):  
Xiyun Deng ◽  
Hirotsugu Ueda ◽  
Shao Bo Su ◽  
Wanghua Gong ◽  
Nancy M. Dunlop ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
G Protein ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Synthetic Peptide ◽  
Immunodeficiency Virus ◽  
And Function ◽  
G Protein Coupled ◽  
Hiv 1

Because envelope gp120 of various strains of human immunodeficiency virus type 1 (HIV-1) downregulates the expression and function of a variety of chemoattractant receptors through a process of heterologous desensitization, we investigated whether epitopes derived from gp120 could mimic the effect. A synthetic peptide domain, designated F peptide, corresponding to amino acid residues 414-434 in the V4-C4 region of gp120 of the HIV-1 Bru strain, potently reduced monocyte binding and chemotaxis response to macrophage inflammatory protein 1β (MIP-1β) and stromal cell-derived factor 1 (SDF-1), chemokines that use the receptors CCR5 and CXCR4, respectively. Further study showed that F peptide by itself is an inducer of chemotaxis and calcium mobilization in human monocytes and neutrophils. In cross-desensitization experiments, among the numerous chemoattractants tested, only the bacterial chemotactic peptide fMLF, when used at high concentrations, partially attenuated calcium mobilization induced by F peptide in phagocytes, suggesting that this peptide domain might share a 7-transmembrane, G-protein–coupled receptor with fMLF. By using cells transfected with cDNAs encoding receptors that interact with fMLF, we found that F peptide uses an fMLF receptor variant, FPRL1, as a functional receptor. The activation of monocytes by F peptide resulted in downregulation of the cell surface expression of CCR5 and CXCR4 in a protein kinase C-dependent manner. These results demonstrate that activation of FPRL1 on human moncytes by a peptide domain derived from HIV-1 gp120 could lead to desensitization of cell response to other chemoattractants. This may explain, at least in part, the initial activation of innate immune responses in HIV-1–infected patients followed by immune suppression.

scholarly journals Evolution-Guided Structural and Functional Analyses of the HERC Family Reveal an Ancient Marine Origin and Determinants of Antiviral Activity

2018 ◽  
Vol 92 (13) ◽  
pp. e00528-18 ◽  
Author(s):  
Ermela Paparisto ◽  
Matthew W. Woods ◽  
Macon D. Coleman ◽  
Seyed A. Moghadasi ◽  
Divjyot S. Kochar ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Particle Production ◽  
Structural Topology ◽  
Antiviral Protein ◽  
Intrinsic Immunity ◽  
Marine Origin ◽  
Immunodeficiency Virus ◽  
And Function ◽  
Functional Analyses ◽  
Hiv 1

ABSTRACTIn humans, homologous to the E6-AP carboxyl terminus (HECT) and regulator of chromosome condensation 1 (RCC1)-like domain-containing protein 5 (HERC5) is an interferon-induced protein that inhibits replication of evolutionarily diverse viruses, including human immunodeficiency virus type 1 (HIV-1). To better understand the origin, evolution, and function of HERC5, we performed phylogenetic, structural, and functional analyses of the entire human small-HERC family, which includes HERC3, HERC4, HERC5, and HERC6. We demonstrated that theHERCfamily emerged >595 million years ago and has undergone gene duplication and gene loss events throughout its evolution. The structural topology of the RCC1-like domain and HECT domains from all HERC paralogs is highly conserved among evolutionarily diverse vertebrates despite low sequence homology. Functional analyses showed that the human small HERCs exhibit different degrees of antiviral activity toward HIV-1 and that HERC5 provides the strongest inhibition. Notably, coelacanth HERC5 inhibited simian immunodeficiency virus (SIV), but not HIV-1, particle production, suggesting that the antiviral activity of HERC5 emerged over 413 million years ago and exhibits species- and virus-specific restriction. In addition, we showed that both HERC5 and HERC6 are evolving under strong positive selection, particularly blade 1 of the RCC1-like domain, which we showed is a key determinant of antiviral activity. These studies provide insight into the origin, evolution, and biological importance of the human restriction factor HERC5 and the other HERC family members.IMPORTANCEIntrinsic immunity plays an important role as the first line of defense against viruses. Studying the origins, evolution, and functions of proteins responsible for effecting this defense will provide key information about virus-host relationships that can be exploited for future drug development. We showed that HERC5 is one such antiviral protein that belongs to an evolutionarily conserved family of HERCs with an ancient marine origin. Not all vertebrates possess all HERC members, suggesting that different HERCs emerged at different times during evolution to provide the host with a survival advantage. Consistent with this, two of the more recently emerged HERC members, HERC5 and HERC6, displayed strong signatures of having been involved in an ancient evolutionary battle with viruses. Our findings provide new insights into the evolutionary origin and function of the HERC family in vertebrate evolution, identifying HERC5 and possibly HERC6 as important effectors of intrinsic immunity in vertebrates.

scholarly journals HTLV-1, HIV-1, hepatitis B and hepatitis delta in the Pacific and South-East Asia: a serological survey

1988 ◽  
Vol 100 (1) ◽  
pp. 153-156 ◽  
Author(s):  
R. J. Brindle ◽  
R. P. Eglin ◽  
A. J. Parsons ◽  
A. V. S. Hill ◽  
J. B. Selkon
Keyword(s):  
Hepatitis B ◽  
East Asia ◽  
South East Asia ◽  
Hepatitis Delta ◽  
Human T Cell ◽  
The Pacific ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Hiv 1

SUMMARYBlood samples from 13 locations in the Pacific and South-East Asia were tested for evidence of infection with human T-cell lymphotropic virus type-1 (HTLV-1), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) and hepatitis delta virus (HDV). No samples were positive for antibody to HIV-1. Antibodies to HTLV-1 were found in samples from five locations, the maximum prevalence being 19%, in Vanuatu. Serological markers of HBV infection were found in all locations, the maximal prevalence being 88%, in Majuro, Micronesia. Antibodies to HDV in HBsAg positive sera were found in six locations with a maximum prevalence of 81% in Kiribati.

Sign in / Sign up

Export Citation Format

Share Document