High Degree of Sensitivity of the Simian Immunodeficiency Virus (SIVmac) Envelope Glycoprotein Subunit Association to Amino Acid Changes in the Glycoprotein 41 Ectodomain

1997 ◽  
Vol 13 (6) ◽  
pp. 441-447 ◽  
Author(s):  
LUISA MARCON ◽  
JOSEPH SODROSKI
Keyword(s):  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Immunodeficiency Virus ◽  
High Degree

scholarly journals Specificity and Neutralizing Capacity of Three Monoclonal Antibodies Produced against the Envelope Glycoprotein of Simian Immunodeficiency Virus Isolate 251

Virology ◽  
1995 ◽  
Vol 211 (1) ◽  
pp. 339-344 ◽  
Author(s):  
Tahar Babas ◽  
Besma Belhadj-Jrad ◽  
Roger Le Grand ◽  
Dominique Dormont ◽  
Luc Montagnier ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Simian Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Virus Isolate ◽  
Neutralizing Capacity ◽  
Immunodeficiency Virus

scholarly journals TRIM5α Resistance Escape Mutations in the Capsid Are Transferable between Simian Immunodeficiency Virus Strains

2016 ◽  
Vol 90 (24) ◽  
pp. 11087-11095 ◽  
Author(s):  
Fan Wu ◽  
Andrea Kirmaier ◽  
Ellen White ◽  
Ilnour Ourmanov ◽  
Sonya Whitted ◽  
...  
Keyword(s):  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Hiv Vaccine ◽  
Sooty Mangabey ◽  
Virus Acquisition ◽  
Vaccine Trials ◽  
Immunodeficiency Virus ◽  
Distinct Strain ◽  
Virus Strains

ABSTRACT TRIM5α polymorphism limits and complicates the use of simian immunodeficiency virus (SIV) for evaluation of human immunodeficiency virus (HIV) vaccine strategies in rhesus macaques. We previously reported that the TRIM5α-sensitive SIV from sooty mangabeys (SIVsm) clone SIVsmE543-3 acquired amino acid substitutions in the capsid that overcame TRIM5α restriction when it was passaged in rhesus macaques expressing restrictive TRIM5α alleles. Here we generated TRIM5α-resistant clones of the related SIVsmE660 strain without animal passage by introducing the same amino acid capsid substitutions. We evaluated one of the variants in rhesus macaques expressing permissive and restrictive TRIM5α alleles. The SIVsmE660 variant infected and replicated in macaques with restrictive TRIM5α genotypes as efficiently as in macaques with permissive TRIM5α genotypes. These results demonstrated that mutations in the SIV capsid can confer SIV resistance to TRIM5α restriction without animal passage, suggesting an applicable method to generate more diverse SIV strains for HIV vaccine studies. IMPORTANCE Many strains of SIV from sooty mangabey monkeys are susceptible to resistance by common rhesus macaque TRIM5α alleles and result in reduced virus acquisition and replication in macaques that express these restrictive alleles. We previously observed that spontaneous variations in the capsid gene were associated with improved replication in macaques, and the introduction of two amino acid changes in the capsid transfers this improved replication to the parent clone. In the present study, we introduced these mutations into a related but distinct strain of SIV that is commonly used for challenge studies for vaccine trials. These mutations also improved the replication of this strain in macaques with the restrictive TRIM5α genotype and thus will eliminate the confounding effects of TRIM5α in vaccine studies.

scholarly journals Compensatory Substitutions Restore Normal Core Assembly in Simian Immunodeficiency Virus Isolates with Gag Epitope Cytotoxic T-Lymphocyte Escape Mutations

2006 ◽  
Vol 80 (16) ◽  
pp. 8168-8177 ◽  
Author(s):  
Wendy W. Yeh ◽  
Evan M. Cale ◽  
Pimkwan Jaru-Ampornpan ◽  
Carol I. Lord ◽  
Fred W. Peyerl ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
Structural Integrity ◽  
Viral Escape ◽  
Amino Acid Substitutions ◽  
Structural Constraints ◽  
Immunodeficiency Virus ◽  
Dominant Epitope

ABSTRACT The evolution of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) as they replicate in infected individuals reflects a balance between the pressure on the virus to mutate away from recognition by dominant epitope-specific cytotoxic T lymphocytes (CTL) and the structural constraints on the virus' ability to mutate. To gain a further understanding of the strategies employed by these viruses to maintain replication competency in the face of the intense selection pressure exerted by CTL, we have examined the replication fitness and morphological ramifications of a dominant epitope mutation and associated flanking amino acid substitutions on the capsid protein (CA) of SIV/simian-human immunodeficiency virus (SHIV). We show that a residue 2 mutation in the immunodominant p11C, C-M epitope (T47I) of SIV/SHIV not only decreased CA protein expression and viral replication, but it also blocked CA assembly in vitro and virion core condensation in vivo. However, these defects were restored by the introduction of upstream I26V and/or downstream I71V substitutions in CA. These findings demonstrate how flanking compensatory amino acid substitutions can facilitate viral escape from a dominant epitope-specific CTL response through the effects of these associated mutations on the structural integrity of SIV/SHIV.

scholarly journals Assorted Mutations in the Envelope Gene of Simian Immunodeficiency Virus Lead to Loss of Neutralization Resistance against Antibodies Representing a Broad Spectrum of Specificities

2003 ◽  
Vol 77 (18) ◽  
pp. 9993-10003 ◽  
Author(s):  
Welkin E. Johnson ◽  
Hannah Sanford ◽  
Linda Schwall ◽  
Dennis R. Burton ◽  
Paul W. H. I. Parren ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
Relative Sensitivity ◽  
Viral Envelope ◽  
Envelope Gene ◽  
Attachment Sites ◽  
Immunodeficiency Virus ◽  
Increased Sensitivity

ABSTRACT Simian immunodeficiency virus (SIV) of macaques isolate SIVmac239 is highly resistant to neutralization by polyclonal antisera or monoclonal antibodies, a property that it shares with most primary isolates of human immunodeficiency virus type 1 (HIV-1). This resistance is important for the ability of the virus to persist at high levels in vivo. To explore the physical features of the viral envelope complex that contribute to the neutralization-resistant phenotype, we examined a panel of SIVmac239 derivatives for sensitivity to neutralization by a large collection of monoclonal antibodies (MAbs). These MAbs recognize both linear and conformational epitopes throughout the viral envelope proteins. The variant viruses included three derivatives of SIVmac239 with substitutions in specific N-linked glycosylation sites of gp120 and a fourth variant that lacked the100 amino acids that encompass the V1 and V2 loops. Also included in this study was SIVmac316, a variant of SIVmac239 with distributed mutations in env that confer significantly increased replicative capacity in tissue macrophages. These viruses were chosen to represent a broad range of neutralization sensitivities based on susceptibility to pooled, SIV-positive plasma. All three of these very different kinds of mutations (amino acid substitutions, elimination of N-glycan attachment sites, and a 100-amino-acid deletion spanning variable loops V1 and V2) dramatically increased sensitivity to neutralization by MAbs from multiple competition groups. Thus, the mutations did not simply expose localized epitopes but rather conferred global increases in neutralization sensitivity. The removal of specific N-glycan attachment sites from V1 and V2 led to increased sensitivity to neutralization by antibodies recognizing epitopes from both within and outside of the V1-V2 sequence. Surprisingly, while most of the mutations that gave rise to increased sensitivity were located in the N-terminal half of gp120 (surface subunit [SU]), the greatest increases in sensitivity were to MAbs recognizing the C-terminal half of gp120 or the ectodomain of gp41 (transmembrane subunit [TM]). This reagent set and information should now be useful for defining the physical, structural, thermodynamic, and kinetic factors that influence relative sensitivity to antibody-mediated neutralization.

Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef

10.1038/15224 ◽  
1999 ◽  
Vol 5 (11) ◽  
pp. 1270-1276 ◽  
Author(s):  
David T. Evans ◽  
David H. O'Connor ◽  
Peicheng Jing ◽  
John L. Dzuris ◽  
John Sidney ◽  
...  
Keyword(s):  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Amino Acid Variation ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses
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