IGHV1, IGHV5 and IGHV7 subgroup genes in the Rhesus macaque

Bible, Jon M.; Howard, Wendy A.; Robbins, Helena; Dunn‐Walters, Deborah K.

doi:10.1007/s00251-003-0536-2

Cited by 34 publications

(28 citation statements)

References 23 publications

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“…The lower map illustrates the presence of rare genes/alleles that are yet to be identified in genetically diverse species. ( b ) Number of VH genes and alleles in human and mouse that are denoted as functional according to the IMGT database and the available set of published rhesus VH genes (August 2016) compiled from published sources314344. *Rhesus sequences may be either genes or alleles.…”

Section: Figurementioning

confidence: 99%

“…Venn diagrams comparing the number and identity of alleles output by IgDiscover when the following series of starting databases or conditions are utilized: ( a ) Public RM VH database constructed from previously published rhesus germline V sequences19434445 versus ‘Single gene RM VH' database, a VH database containing a single sequence, (VH7.21). ( b ) Public RM VH database versus ‘Mutated Public RM VH database', a database created by randomly mutating 10 bases in every sequence within the Public RM VH database.…”

Section: Figurementioning

confidence: 99%

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Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

et al. 2016

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Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

et al. 2016

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“…However, the number of functional RM germline V H sequences in the IMGT database (n=23) was disproportionately low compared to the human sequences (n=53; Supplementary Table 2). Mining of the currently available RM IgH locus (Gibbs et al 2007) revealed 61 RM V H genes (Sundling et al 2012), but functional V H germline sequences (n=89) from several studies (Andris et al 1997; Bible et al 2003; Helmuth et al 2000) were also compiled in the King’s College RM Ig Gene Database (http://www.kcl.ac.uk/immunobiology/Mac_ig/). …”

Section: Resultsmentioning

confidence: 99%

“…However, the impact of SIV infection on the overall RM Ab repertoire remains unknown. Here, we utilized RM V H genes mined from published sources (Andris et al 1997; Bible et al 2003; Helmuth et al 2000; Sundling et al 2012) as well as pre-infection IgM sequences to quantify V H gene repertoire changes and mutation rates. Using the SIV-RM model, we now provide a potential timetable for SHM changes during pathogenic lentivirus infection.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we utilized available RM V H germline sequences (Andris et al 1997; Bible et al 2003; Helmuth et al 2000; Olivieri and Gambon-Deza 2015; Sundling et al 2012) primarily mined from the RM genome sequence (Gibbs et al 2007) and adopted a next-generation sequencing (NGS) strategy to quantify Ig SHM. We provide, to our knowledge, the first longitudinal analysis of IgG V H gene distribution and SHM rates of RMs infected with SIV using an NGS strategy.…”

Section: Introductionmentioning

confidence: 99%

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Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection of rhesus macaques

et al. 2015

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B cell functional defects are associated with delayed neutralizing antibody development in pathogenic lentivirus infections. However, the timeframe for alterations in the antibody repertoire and somatic hypermutation (SHM) remains unclear. Here, we utilized the SIV/rhesus macaque (RM) model to investigate the dynamics of immunoglobulin VH gene diversity and SHM following infection. Three RMs were infected with SIVmac239 and VH1, VH3 and VH4 genes were amplified from peripheral blood at 0, 2, 6, 24 and 36 weeks post-infection for next-generation sequencing. Analysis of over 3.8 million sequences against currently available RM germline VH genes revealed a highly biased VH gene repertoire in outbred RMs. SIV infection did not significantly perturb the predominant IgG1 response, but overall immunoglobulin SHM declined during the course of SIV infection. Moreover, SHM at the AID deamination hotspot, WRC, rapidly decreased and was suppressed throughout SIV infection. In contrast, a transient increase in mutations at the APOBEC3G deamination hotspot, CCC, coincided with a spike in APOBEC3G expression during acute SIV infection. The results outline a timetable for altered VH gene repertoire and IgG SHM in the SIV/RM model and suggest a burst of APOBEC3G-mediated antibody SHM during acute SIV infection.

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Nonhuman Primate Models for HIV/AIDS Vaccine Development

et al. 2013

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The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

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IGHV1, IGHV5 and IGHV7 subgroup genes in the Rhesus macaque

Cited by 34 publications

References 23 publications

Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection of rhesus macaques

Nonhuman Primate Models for HIV/AIDS Vaccine Development

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