Chimeric HIV-1 and feline immunodeficiency virus reverse transcriptases: critical role of the p51 subunit in the structural integrity of heterodimeric lentiviral DNA polymerases

1998 ◽  
Vol 278 (4) ◽  
pp. 757-765 ◽  
Author(s):  
Mario Amacker ◽  
Ulrich Hübscher
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Structural Integrity ◽  
Dna Polymerases ◽  
Critical Role ◽  
Reverse Transcriptases ◽  
Immunodeficiency Virus ◽  
Hiv 1

Retrovirus Reverse Transcriptases Containing a Modified YXDD Motif

2005 ◽  
Vol 16 (3) ◽  
pp. 169-182 ◽  
Author(s):  
Prem L Sharma ◽  
Viktoria Nurpeisov ◽  
Raymond F Schinazi
Keyword(s):  
Amino Acid ◽  
Feline Immunodeficiency Virus ◽  
Dna Polymerases ◽  
Viral Pathogenesis ◽  
Virus Infectivity ◽  
Leukaemia Virus ◽  
Reverse Transcriptases ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

The YXDD motif, where X is a variable amino acid, is highly conserved among various viral RNA-dependent DNA polymerases. Mutations in the YXDD motif can abolish enzymatic activity, alter the processivity and fidelity of enzymes and decrease virus infectivity. This review provides a summary of the significant documented studies on the YXDD motif of HIV-1, simian immunodeficiency virus, feline immunodeficiency virus and murine leukaemia virus and the impact of mutation that this motif has had on viral pathogenesis and drug treatment.

Anatomy and pathology of HIV-1 peptidase

2002 ◽  
Vol 38 ◽  
pp. 113-127 ◽  
Author(s):  
Ben M Dunn
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Drug Target ◽  
Concerted Effort ◽  
Drug Pressure ◽  
The Past ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Hiv 1

The peptidase of the HIV type 1 (HIV PR) is required for the replication of and further infection by the virus. A concerted effort has taken place in the past 15 years to understand the properties of this enzyme, as it serves as an excellent drug target for control of the virus. Owing to drug pressure, many mutations arise during turnover of the virus and some of these lead to resistance to the effects of the inhibitors. Recent advances in the understanding of the changes these mutations cause to the enzyme and its interaction with substrates and inhibitors have been described. In addition, studies of closely related retroviral enzymes from simian immunodeficiency virus, feline immunodeficiency virus and HIV-2 have expanded the structure-function paradigm. The role of the flexibility of ligands and of the enzyme in active-site interactions is discussed.

scholarly journals Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

2009 ◽  
Vol 90 (8) ◽  
pp. 1795-1805 ◽  
Author(s):  
Bizhan Romani ◽  
Susan Engelbrecht
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Critical Role ◽  
Cellular Proteins ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of cellular and viral proteins. The functions of many of these interactions in the pathogenesis of HIV-1 have been identified. Deletion of the vpr gene reduces the virulence of HIV-1 dramatically, indicating the importance of this protein for the virus. This review describes the current findings on several established functions of HIV-1 Vpr and some possible roles proposed for this protein. Because Vpr exploits cellular proteins and pathways to influence the biology of HIV-1, understanding the functions of Vpr usually involves the study of cellular pathways. Several functions of Vpr are attributed to the virion-incorporated protein, but some of them are attributed to the expression of Vpr in HIV-1-infected cells. The structure of Vpr may be key to understanding the variety of its interactions. Due to the critical role of Vpr in HIV-1 pathogenicity, study of the interactions between Vpr and cellular proteins may help us to understand the mechanism(s) of HIV-1 pathogenicity.

scholarly journals Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jennifer L Elliott ◽  
Jenna E Eschbach ◽  
Pratibha C Koneru ◽  
Wen Li ◽  
Maritza Puray-Chavez ◽  
...  
Keyword(s):  
Rna Binding ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Class Ii ◽  
Viral Rna ◽  
Target Cells ◽  
Ribonucleoprotein Complexes ◽  
Immunodeficiency Virus ◽  
Hiv 1

A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional IN multimerization. Inhibition of IN-RNA interactions resulted in the mislocalization of viral ribonucleoprotein complexes outside the capsid lattice, which led to premature degradation of the viral genome and IN in target cells. Collectively, our studies uncover causal mechanisms for the class II phenotype and highlight an essential role of IN-RNA interactions for accurate virion maturation.

scholarly journals Alteration of Substrate and Inhibitor Specificity of Feline Immunodeficiency Virus Protease

2000 ◽  
Vol 74 (10) ◽  
pp. 4710-4720 ◽  
Author(s):  
Ying-Chuan Lin ◽  
Zachary Beck ◽  
Taekyu Lee ◽  
Van-Duc Le ◽  
Garrett M. Morris ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Feline Immunodeficiency Virus ◽  
Critical Role ◽  
Phage Display Library ◽  
Hiv Protease ◽  
Wild Type ◽  
Inhibitor Specificity ◽  
Immunodeficiency Virus ◽  
Reduced Activity ◽  
Hiv 1

ABSTRACT Feline immunodeficiency virus (FIV) protease is structurally very similar to human immunodeficiency virus (HIV) protease but exhibits distinct substrate and inhibitor specificities. We performed mutagenesis of subsite residues of FIV protease in order to define interactions that dictate this specificity. The I37V, N55M, M56I, V59I, and Q99V mutants yielded full activity. The I37V, N55M, V59I, and Q99V mutants showed a significant increase in activity against the HIV-1 reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type (wt) FIV protease. The I37V, V59I, and Q99V mutants also showed an increase in activity against two rapidly cleaved peptides selected by cleavage of a phage display library with HIV-1 protease. Mutations at Q54K, I98P, and L101I dramatically reduced activity. Mutants containing a I35D or I57G substitution showed no activity against either FIV or HIV substrates. FIV proteases all failed to cut HIV-1 matrix/capsid, P1/P6, P6/protease, and protease/reverse transcriptase junctions, indicating that none of the substitutions were sufficient to change the specificity completely. The I37V, N55M, M56I, V59I, and Q99V mutants, compared with wt FIV protease, all showed inhibitor specificity more similar to that of HIV-1 protease. The data also suggest that FIV protease prefers a hydrophobic P2/P2′ residue like Val over Asn or Glu, which are utilized by HIV-1 protease, and that S2/S2′ might play a critical role in distinguishing FIV and HIV-1 protease by specificity. The findings extend our observations regarding the interactions involved in substrate binding and aid in the development of broad-based inhibitors.

scholarly journals Effect of Mutations in the Second Extracellular Loop of CXCR4 on Its Utilization by Human and Feline Immunodeficiency Viruses

1999 ◽  
Vol 73 (4) ◽  
pp. 2576-2586 ◽  
Author(s):  
Anne Brelot ◽  
Nikolaus Heveker ◽  
Karen Adema ◽  
Margaret J. Hosie ◽  
Brian Willett ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Negative Charge ◽  
Extracellular Loop ◽  
Specific Effects ◽  
Immunodeficiency Virus ◽  
Different Types ◽  
Arginine Residues ◽  
Hiv 1

ABSTRACT CCR5 and CXCR4 are the principal CD4-associated coreceptors used by human immunodeficiency virus type 1 (HIV-1). CXCR4 is also a receptor for the feline immunodeficiency virus (FIV). The rat CXCR4 cannot mediate infection by HIV-1NDK or by FIVPET(both cell line-adapted strains) because of sequence differences with human CXCR4 in the second extracellular loop (ECL2). Here we made similar observations for HIV-189.6 (a strain also using CCR5) and for a primary HIV-1 isolate. It showed the role of ECL2 in the coreceptor activity of CXCR4 for different types of HIV-1 strains. By exchanging ECL2 residues between human and rat CXCR4, we found that several amino acid differences contributed to the inactivity of the rat CXCR4 toward HIV-189.6. In contrast, its inactivity toward HIV-1NDK seemed principally due to a serine at position 193 instead of to an aspartic acid (Asp193) in human CXCR4. Likewise, a mutation of Asp187 prevented usage of CXCR4 by FIVPET. Different mutations of Asp193, including its replacement by a glutamic acid, markedly reduced or suppressed the activity of CXCR4 for HIV-1NDK infection, indicating that the negative charge was not the only requirement. Mutations of Asp193 and of arginine residues (Arg183 and Arg188) of CXCR4 reduced the efficiency of HIV-1 infection for all HIV-1 strains tested. Other ECL2 mutations tested had strain-specific effects or no apparent effect on HIV-1 infection. The ECL2 mutants allowed us to identify residues contributing to the epitope of the 12G5 monoclonal antibody. Overall, residues with different charges and interspersed in ECL2 seem to participate in the coreceptor activity of CXCR4. This suggests that a conformational rather than linear epitope of ECL2 contributes to the HIV-1 binding site. However, certain HIV-1 and FIV strains seem to require the presence of a particular ECL2 residue.

scholarly journals Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Expression Profiles ◽  
Critical Role ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Target Mrnas ◽  
Immunodeficiency Virus ◽  
Mirna Sequencing ◽  
Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

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