scholarly journals A Specific Region of 37 Amino Acid Residues in the SPRY (B30.2) Domain of African Green Monkey TRIM5α Determines Species-Specific Restriction of Simian Immunodeficiency Virus SIVmac Infection

2005 ◽  
Vol 79 (14) ◽  
pp. 8870-8877 ◽  
Author(s):  
Emi E. Nakayama ◽  
Hiroyuki Miyoshi ◽  
Yoshiyuki Nagai ◽  
Tatsuo Shioda
Keyword(s):  
Amino Acid ◽  
Cell Line ◽  
Specific Region ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Green Monkey ◽  
Specific Restriction ◽  
Species Specific ◽  
Hiv 1 ◽  
B30.2 Domain

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) efficiently enters cells of Old World monkeys but encounters a block before reverse transcription. This restriction is mediated by a dominant repressive factor. Recently, a member of the tripartite motif (TRIM) family proteins, TRIM5α, was identified as a blocking factor in a rhesus macaque cDNA library. Among Old World monkey cell lines, the African green monkey kidney cell line CV1 is highly resistant to not only HIV-1 but also simian immunodeficiency virus SIVmac infection. We analyzed TRIM5α of CV1 cells and HSC-F cells, a T-cell line from a cynomolgus monkey, and found that both CV1- and HSC-F-TRIM5αs could inhibit CD4-dependent HIV-1 infection, as well as vesicular stomatitis virus glycoprotein-mediated infection. CV1-TRIM5α could also inhibit SIVmac infection, whereas HSC-F-TRIM5α could not. In the SPRY (B30.2) domain of CV1-TRIM5α, there was a 20-amino-acid duplication that was not present in HSC-F-TRIM5α. A chimeric TRIM5α containing 37 amino acid residues from CV1-TRIM5α, which spanned the 20-amino-acid duplication, in the background of HSC-F-TRIM5α fully gained the ability to inhibit SIVmac infection. Conversely, the mutant CV1-TRIM5α lacking the 20-amino-acid duplication completely lost the ability to restrict SIVmac infection. These findings clearly indicated that a specific region of 37 amino acid residues in the SPRY domain of CV1-TRIM5α contained a determinant of species-specific restriction of SIVmac.

scholarly journals Efficacy of Dideoxynucleosides against Human Foamy Virus and Relationship to Its Reverse Transcriptase Amino Acid Sequence and Structure

2001 ◽  
Vol 75 (15) ◽  
pp. 7184-7187 ◽  
Author(s):  
Anne Yvon-Groussin ◽  
Pierre Mugnier ◽  
Philippe Bertin ◽  
Marc Grandadam ◽  
Henri Agut ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Foamy Virus ◽  
Three Dimensional ◽  
Retroviral Vectors ◽  
Dimensional Structure ◽  
Human Foamy Virus ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human foamy virus (HFV), a retrovirus of simian origin which occasionally infects humans, is the basis of retroviral vectors in development for gene therapy. Clinical considerations of how to treat patients developing an uncontrolled infection by either HFV or HFV-based vectors need to be raised. We determined the susceptibility of the HFV to dideoxynucleosides and found that only zidovudine was equally efficient against the replication of human immunodeficiency virus type 1 (HIV-1) and HFV. By contrast, zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), and didanosine (ddI) were 3-, 3-, 30-, and 46-fold less efficient against HFV than against HIV-1, respectively. Some amino acid residues known to be involved in HIV-1 resistance to ddC, 3TC, d4T, and ddI were found at homologous positions of HFV reverse transcriptase (RT). These critical amino acids are located at the same positions in the three-dimensional structure of HIV-1 and HFV RT, suggesting that both enzymes share common patterns of inhibition.

scholarly journals The HIV-1 Vpu transmembrane domain topology and formation of a hydrophobic interface with BST-2 are critical for Vpu-mediated BST-2 downregulation

2020 ◽  
Author(s):  
Nabab Khan ◽  
Siladitya Padhi ◽  
Paresh Patel ◽  
U. Deva Priyakumar ◽  
Shahid Jameel
Keyword(s):  
Amino Acid ◽  
Transmembrane Domain ◽  
Virus Production ◽  
Cell Protein ◽  
Amino Acid Residues ◽  
Host Cell Protein ◽  
Immunodeficiency Virus ◽  
Molecular Modeling Studies ◽  
Hiv 1 ◽  
Hydrophobic Interface

AbstractViruses belonging to the M group of human immunodeficiency virus (HIV-1) are the most virulent among the four HIV-1 groups. One factor that distinguishes the M group HIV-1 from others is Vpu, a membrane localized accessory protein, which promotes the release of virions by neutralizing the antiviral host cell protein BST-2. To investigate if this activity is determined by the topology of Vpu or by conserved amino acid residues, we prepared chimeric forms of Vpu by replacing its transmembrane domain with those from its topological homologs. Although the chimeric Vpu proteins downregulated BST-2, these substantially reduced virus production as well. Molecular modeling studies on Vpu from different HIV-1 groups and the chimeric Vpu proteins showed that shape and the availability of a hydrophobic interface are more important for BST-2 antagonism than conservation of the amino acid sequence. Our data suggest that the HIV-1 Vpu-M protein has evolved topologically to interact with BST-2, and that the Vpu/BST-2 interface can be exploited as a target to limit HIV-1 replication.

scholarly journals Role of the Membrane-Spanning Domain of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein in Cell-Cell Fusion and Virus Infection

2008 ◽  
Vol 82 (11) ◽  
pp. 5417-5428 ◽  
Author(s):  
Liang Shang ◽  
Ling Yue ◽  
Eric Hunter
Keyword(s):  
Amino Acid ◽  
Cell Fusion ◽  
Viral Entry ◽  
Envelope Glycoprotein ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Membrane Spanning ◽  
Hiv 1

ABSTRACT The membrane-spanning domain (MSD) of the human immunodeficiency virus type 1 (HIV-1) gp41 glycoprotein is critical for its biological activity. Previous C-terminal truncation studies have predicted an almost invariant core structure of 12 amino acid residues flanked by basic amino acids in the HIV-1 MSD that function to anchor the glycoprotein in the lipid bilayer. To further understand the role of specific amino acids within the MSD core, we initially replaced the core region with 12 leucine residues and then constructed recovery-of-function mutants in which specific amino acid residues (including a GGXXG motif) were reintroduced. We show here that conservation of the MSD core sequence is not required for normal expression, processing, intracellular transport, and incorporation into virions of the envelope glycoprotein (Env). However, the amino acid composition of the MSD core does influence the ability of Env to mediate cell-cell fusion and plays a critical role in the infectivity of HIV-1. Replacement of conserved amino acid residues with leucine blocked virus-to-cell fusion and subsequent viral entry into target cells. This restriction could not be released by C-terminal truncation of the gp41 glycoprotein. These studies imply that the highly conserved core residues of the HIV Env MSD, in addition to serving as a membrane anchor, play an important role in mediating membrane fusion during viral entry.

scholarly journals Vif of Feline Immunodeficiency Virus from Domestic Cats Protects against APOBEC3 Restriction Factors from Many Felids

2010 ◽  
Vol 84 (14) ◽  
pp. 7312-7324 ◽  
Author(s):  
Jörg Zielonka ◽  
Daniela Marino ◽  
Henning Hofmann ◽  
Naoya Yuhki ◽  
Martin Löchelt ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Domestic Cat ◽  
Moderate Degree ◽  
Restriction Factors ◽  
Cytidine Deaminases ◽  
Immunodeficiency Virus ◽  
Specific Restriction ◽  
Species Specific ◽  
Vif Protein ◽  
Hiv 1

ABSTRACT To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Δvif FIV, felid A3Z2s did not show any antiviral activity against Δvif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether VifFIV can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.VifFIV was constructed. This HIV-1.VifFIV was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

scholarly journals T134, a Small-Molecule CXCR4 Inhibitor, Has No Cross-Drug Resistance with AMD3100, a CXCR4 Antagonist with a Different Structure

1999 ◽  
Vol 73 (2) ◽  
pp. 1719-1723 ◽  
Author(s):  
Rieko Arakaki ◽  
Hirokazu Tamamura ◽  
Mariappan Premanathan ◽  
Kenji Kanbara ◽  
Sivasundaram Ramanan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mononuclear Cells ◽  
Target Cells ◽  
Amino Acid Residues ◽  
Cxcr4 Antagonist ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Stromal Cell Derived Factor ◽  
Hiv 1

ABSTRACT T22, an analog of polyphemusin II (18 amino acid residues), was found to block T-tropic human immunodeficiency virus type 1 (HIV-1) entry into target cells as a CXCR4 inhibitor. We synthesized T134, a small analog (14 amino acid residues) of T22 with reduced positive charges. T134 exhibited highly potent activity and significantly less cytotoxicity in comparison to that of T22. T134 prevents the anti-CXCR4 monoclonal antibody from binding to peripheral blood mononuclear cells but has no effect on the binding of anti-CCR5 monoclonal antibodies. Since T134 inhibits the binding of stromal cell-derived factor-1 (SDF-1) to MT-4 cells, it seems that T134 prevents HIV-1 entry by binding to CXCR4. The bicyclam AMD3100 has also been shown to block HIV-1 entry via CXCR4 but not via CCR5. Both T134 and AMD3100 are CXCR4 antagonists and low-molecular-weight compounds but have different structures. Our results indicate that T134 is active against wild-type T-tropic HIV-1 strains and against AMD3100-resistant strains.

scholarly journals Amino Acid Residues 88 and 89 in the Central Hydrophilic Region of Human Immunodeficiency Virus Type 1 Vif Are Critical for Viral Infectivity by Enhancing the Steady-State Expression of Vif

2003 ◽  
Vol 77 (2) ◽  
pp. 1626-1632 ◽  
Author(s):  
Mikako Fujita ◽  
Akiko Sakurai ◽  
Akiko Yoshida ◽  
Maki Miyaura ◽  
A. Hajime Koyama ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Amino Acid ◽  
Virus Replication ◽  
Viral Infectivity ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Hydrophilic Region ◽  
Hiv 1

ABSTRACT A hydrophilic region consisting of strikingly clustered charged amino acids is present at the center of human immunodeficiency virus type 1 (HIV-1) Vif. In this study, the role for this central hydrophilic region (E88WRKKR93) in the virus replication in nonpermissive H9 cells was investigated by extensive deletion and substitution analysis. A total of 31 mutants were constructed. Deletion of the E88 or W89 residue alone abolished viral infectivity in H9 cells and impaired virus replication in primary macrophage cultures. Substitution analysis indicated that the hydrophilicity and charge of the central region are insignificant for the function of Vif. Of the 16 substitution mutants, 3 mutants with substitution of E88 and W89 with an A residue did not grow in H9 cells. Upon transfection, four mutants (i.e., two mutants with deletion of E88 or W89; a mutant with substitution of E88 and W89 with A; and a mutant with substitution of E88, W89, and R90 with A) were found to express Vif at a very reduced level relative to that by the wild-type clone. These results have thus demonstrated that amino acid residues 88 and 89 of Vif are critical for the replication of HIV-1 in target cells by enhancing the steady-state expression of Vif. In addition, E88 and W89 residues were found to be extremely conserved among the Vif proteins of naturally occurring HIV-1 field isolates as well as those of laboratory HIV-1 strains.

scholarly journals Vpu of a Simian Immunodeficiency Virus Isolated from Greater Spot-Nosed Monkey Antagonizes Human BST-2 via Two AxxxxxxxW Motifs

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Weitong Yao ◽  
Takeshi Yoshida ◽  
Saki Hashimoto ◽  
Hiroaki Takeuchi ◽  
Klaus Strebel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Selective Advantage ◽  
Genetic Alterations ◽  
Amino Acid Sequences ◽  
Virion Release ◽  
Immunodeficiency Virus ◽  
Species Specific ◽  
Hiv 1

ABSTRACT BST-2/CD317/tetherin is a host transmembrane protein that potently inhibits human immunodeficiency virus type 1 (HIV-1) virion release by tethering the nascent virions to the plasma membrane. Viral protein U (Vpu) is an accessory protein encoded by HIV-1 as well as by some simian immunodeficiency viruses (SIVs) infecting wild chimpanzees, gorillas, or monkeys (SIVcpz, SIVgor, or SIVgsn/SIVmon/SIVmus, respectively). HIV-1 Vpu directly binds to and downregulates human BST-2. The antagonism is highly species specific because the amino acid sequences of BST-2 are different among animal species. Here, we show that Vpu proteins from several SIVcpz, SIVgsn, SIVmon, or SIVmus isolates fail to antagonize human BST-2. Only Vpu from an SIVgsn isolate (SIVgsn-99CM71 [SIVgsn71]) was able to antagonize human BST-2 as well as BST-2 of its natural host, greater spot-nosed monkey (GSN). This SIVgsn Vpu interacted with human BST-2, downregulated cell surface human BST-2 expression, and facilitated HIV-1 virion release in the presence of human BST-2. While the unique 14AxxxxxxxW22 motif in the transmembrane domain of HIV-1NL4-3Vpu was reported to be important for antagonizing human BST-2, we show here that two AxxxxxxxW motifs (A22W30 and A25W33) exist in SIVgsn71 Vpu. Only the A22W30 motif was needed for SIVgsn71 Vpu to antagonize GSN BST-2, suggesting that the mechanism of this antagonism resembles that of HIV-1NL4-3 Vpu against human BST-2. Interestingly, SIVgsn71 Vpu requires two AxxxxxxxW (A22W30 and A25W33) motifs to antagonize human BST-2, suggesting an as-yet-undefined way that SIVgsn71 Vpu works against human BST-2. These results imply an evolutionary impact of primate BST-2 on lentiviral Vpu. IMPORTANCE Genetic alterations conferring a selective advantage in protecting from life-threating pathogens are maintained during evolution. In fact, the amino acid sequences of BST-2 differ among primate animals and their susceptibility to viral proteins is species specific, suggesting that such genetic diversity has arisen through the evolutionarily controlled balance between the host and pathogens. The M (main) group of HIV-1 is thought to be derived from SIVcpz, which utilizes Nef, but not Vpu, to antagonize chimpanzee BST-2. SIVcpz Nef is, however, unable to antagonize human BST-2, and Vpu was consequently chosen again as an antagonist against human BST-2 in the context of HIV-1. Studies on how Vpu lost and acquired this ability, together with the distinct mechanisms by which SIVgsn71 Vpu binds to and downregulates human or GSN BST-2, may help to explain the evolution of this lentiviral protein as a result of host-pathogen interactions.

scholarly journals Drug-associated changes in amino acid residues in Gag p2, p7NC, and p6Gag/p6Pol in human immunodeficiency virus type 1 (HIV-1) display a dominant effect on replicative fitness and drug response

Virology ◽  
2008 ◽  
Vol 378 (2) ◽  
pp. 272-281 ◽  
Author(s):  
Sarah K. Ho ◽  
Roxana M. Coman ◽  
Joshua C. Bunger ◽  
Stephanie L. Rose ◽  
Patricia O'Brien ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Response ◽  
Amino Acid Residues ◽  
Dominant Effect ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Structure-Based Mutational Analysis of the C-Terminal DNA-Binding Domain of Human Immunodeficiency Virus Type 1 Integrase: Critical Residues for Protein Oligomerization and DNA Binding

1998 ◽  
Vol 72 (6) ◽  
pp. 4841-4848 ◽  
Author(s):  
Ramon A. Puras Lutzke ◽  
Ronald H. A. Plasterk
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Dna Binding ◽  
Human Immunodeficiency Virus Type ◽  
Mutational Analysis ◽  
Amino Acid Residues ◽  
Terminal Domain ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The C-terminal domain of human immunodeficiency virus type 1 (HIV-1) integrase (IN) is a dimer that binds to DNA in a nonspecific manner. The structure of the minimal region required for DNA binding (IN220–270) has been solved by nuclear magnetic resonance spectroscopy. The overall fold of the C-terminal domain of HIV-1 IN is similar to those of Src homology region 3 domains. Based on the structure of IN220–270, we studied the role of 15 amino acid residues potentially involved in DNA binding and oligomerization by mutational analysis. We found that two amino acid residues, arginine 262 and leucine 234, contribute to DNA binding in the context of IN220–270, as indicated by protein-DNA UV cross-link analysis. We also analyzed mutant proteins representing portions of the full-length IN protein. Amino acid substitution of residues located in the hydrophobic dimer interface, such as L241A and L242A, results in the loss of oligomerization of IN; consequently, the levels of 3′ processing, DNA strand transfer, and intramolecular disintegration are strongly reduced. These results suggest that dimerization of the C-terminal domain of IN is important for correct multimerization of IN.

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