Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

Pahar, Bapi; Kenway-Lynch, Carys S.; Marx, Preston A.; Srivastav, Sudesh; LaBranche, Celia C.; Montefiori, David C.; Das, Arpita

doi:10.1186/s12985-016-0652-x

Cited by 10 publications

(8 citation statements)

References 48 publications

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“…Post-infection samples showed fluorescence intensity as high as 1,000 times the intensity in pre-infection samples (S1 Fig). Regions of higher-fold increases in fluorescence intensity corresponded to previously defined variable domains of env which are known antibody targets, the variable loop regions, as well as others corresponding to known epitopes [42,43]. Taken together, these results validate epitope definition on the peptide microarray platform and show this platform to be capable of high-resolution virus-specific IgG epitope identification using the analytic methods utilized here.…”

Section: Methodssupporting

confidence: 70%

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

et al. 2018

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The specificity of the antibody response against Zika virus (ZIKV) is not well-characterized. This is due, in part, to the antigenic similarity between ZIKV and closely related dengue virus (DENV) serotypes. Since these and other similar viruses co-circulate, are spread by the same mosquito species, and can cause similar acute clinical syndromes, it is difficult to disentangle ZIKV-specific antibody responses from responses to closely-related arboviruses in humans. Here we use high-density peptide microarrays to profile anti-ZIKV antibody reactivity in pregnant and non-pregnant macaque monkeys with known exposure histories and compare these results to reactivity following DENV infection. We also compare cross-reactive binding of ZIKV-immune sera to the full proteomes of 28 arboviruses. We independently confirm a purported ZIKV-specific IgG antibody response targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-infected people and we show that antibody reactivity in pregnant animals can be detected as late as 127 days post-infection (dpi). However, we also show that these responses wane over time, sometimes rapidly, and in one case the response was elicited following DENV infection in a previously ZIKV-exposed animal. These results suggest epidemiologic studies assessing seroprevalence of ZIKV immunity using linear epitope-based strategies will remain challenging to interpret due to susceptibility to false positive results. However, the method used here demonstrates the potential for rapid profiling of proteome-wide antibody responses to a myriad of neglected diseases simultaneously and may be especially useful for distinguishing antibody reactivity among closely related pathogens.

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Section: Methodssupporting

confidence: 70%

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

et al. 2018

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“…Post-infection samples showed fluorescence intensity as high as 1,000 times the intensity in pre-infection samples (Supplemental figure S1). Regions of higher-fold increases in fluorescence intensity corresponded to previously defined variable domains of env which are known antibody targets, the variable loop regions, as well as others corresponding to known epitopes [41,42]. Taken together, these results validate epitope definition on the peptide microarray platform and show this platform to be capable of high-resolution virus-specific IgG epitope identification using the analytic methods utilized here.…”

Section: Methodssupporting

confidence: 70%

“…Serum from two Mauritian cynomolgus macaques (animals A1 and A2) before and after infection with SIVmac239 was evaluated for reactivity to overlapping peptides representing the SIVmac239 env protein sequence on a linear peptide microarray. SIV env variable loop regions [41] are highlighted in grey.…”

Section: Supplemental Materialsmentioning

confidence: 99%

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

Mohr

Heffron

Baker

et al. 2018

Preprint

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24The kinetics and specificity of antibody responses against Zika virus (ZIKV) are not well-25 characterized. This is due, in part, to the antigenic similarity between ZIKV and closely 26 related Dengue virus (DENV) serotypes. Since these and other similar viruses co-27 circulate and are spread by the same mosquito species, it is difficult to disentangle 28 ZIKV-specific antibody responses from responses to closely-related arboviruses in 29 humans. Here we use high-density peptide microarrays to differentiate ZIKV from DENV 30 antibody reactivity in pregnant and non-pregnant macaque monkeys with known 31 exposure histories. We independently confirm a ZIKV-specific IgG antibody response 32 targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-33 infected people and show that antibody reactivity in pregnant animals can be detectable 34 as late as 113 days post-infection (dpi). We also show, however, these responses wane 35 over time, and in one case the response was elicited following DENV infection in a 36 previously ZIKV-exposed animal. The generally weak and short-lived antibody 37 responses to this NS2B epitope, the only reliably ZIKV-specific epitope identified to date 38 to our knowledge, suggest epidemiologic studies assessing seroprevalence specifically 39 to ZIKV using linear epitope-based strategies may be prone to false negative or 40 otherwise confounded results. These results additionally indicate some antibodies 41 produced in response to ZIKV infection are in circulation for only a short period of time. 42 43 IMPORTANCE 44Infection with ZIKV during pregnancy can lead to congenital ZIKV infection and 45 associated birth defects. The vulnerability of communities to future ZIKV outbreaks will 46 . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/352880 doi: bioRxiv preprint first posted online 3 depend, in part, on the prevalence of immunity, which is thought to be mediated 47 principally by antibodies. We currently lack diagnostic assays to differentiate ZIKV-48 specific antibodies from antibodies directed against closely related DENV and we do not 49 know how long anti-ZIKV responses persist. Here we profile antibodies recognizing 50 linear epitopes throughout the entire ZIKV and DENV polyproteins and show that while 51 ZIKV-specific antibody responses can be detected, these responses are generally weak 52 and ephemeral. This may complicate efforts to identify people previously infected with 53 ZIKV and to determine ZIKV seroprevalence, and it raises questions about the utility of 54 linear epitope-based technologies in defining ZIKV infection history. 55 56 INTRODUCTION 57

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“…In our earlier studies we have not detected any association between viral dosage, CD4 depletion, and viral loads in RhMs [ 26 , 27 , 28 ]. Based on the stage of menstrual cycle in female RhMs, the vaginal mucosal may exhibit variation in mucosal thickness and a high single dose is preferred to infect female RhMs [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 83%

Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques

Boby

Ransom

Pace

et al. 2021

Cells

Self Cite

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Transforming growth factor-β signaling (TGF-β) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-β promotes immunosuppression in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-β production that attributes to its pathological manifestations remain unknown. Here, we have shown increased production of TGF-β in a majority of intestinal CD3−CD20−CD68+ cells from acute and chronically SIV infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4+ T cells. No significant changes in intestinal TGF-β receptor II expression were observed but increased production of the pSMAD2/3 protein and SMAD3 gene expression in jejunum tissues that were accompanied by a downregulation of SMAD7 protein and gene expression. Enhanced TGF-β production by intestinal CD3−CD20−CD68+ cells and increased TGF-β/SMAD-dependent signaling might be due to a disruption of a negative feedback loop mediated by SMAD7. This suggests that SIV infection impacts the SMAD-dependent signaling pathway of TGF-β and provides a potential framework for further study to understand the role of viral factor(s) in modulating TGF-β production and downregulating SMAD7 expression in SIV. Regulation of mucosal TGF-β expression by therapeutic TGF-β blockers may help to create effective antiviral mucosal immune responses.

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Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

Cited by 10 publications

References 48 publications

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques

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