Adaptive immune responses in humans during Nipah virus acute and convalescent phases of infection

Research output: Contribution to journalArticle

Abstract

Background
Nipah virus (NiV) is one of ten potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in two human survivors.

Methods
Serial blood samples were obtained from the only two survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T lymphocyte and B lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific IgM and IgG ELISA.

Results
Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. Over 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B lymphocyte, activated B cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells.

Conclusion
We describe for the first time longitudinal kinetic data on the activation status of human B and T cell populations during acute Nipah virus infection. While marked CD8 T cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

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Nipah Virus
Adaptive Immunity
T-Lymphocytes
Infection
B-Lymphocytes
Immunoglobulin G
Humoral Immunity
Viruses
Disease Outbreaks
Immunoglobulin M
Granzymes
Lymphocyte Count
Virus Diseases
India
Flow Cytometry
Emergencies

Cite this

@article{ac456de4997a4e6c96957d36a7026b60,
title = "Adaptive immune responses in humans during Nipah virus acute and convalescent phases of infection",
abstract = "BackgroundNipah virus (NiV) is one of ten potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in two human survivors.MethodsSerial blood samples were obtained from the only two survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T lymphocyte and B lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific IgM and IgG ELISA.ResultsAbsolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. Over 30{\%} of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B lymphocyte, activated B cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells.ConclusionWe describe for the first time longitudinal kinetic data on the activation status of human B and T cell populations during acute Nipah virus infection. While marked CD8 T cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.",
author = "Arunkumar G",
year = "2019",
month = "1",
day = "7",
doi = "10.1093/cid/ciz010",
language = "English",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Adaptive immune responses in humans during Nipah virus acute and convalescent phases of infection

AU - G, Arunkumar

PY - 2019/1/7

Y1 - 2019/1/7

N2 - BackgroundNipah virus (NiV) is one of ten potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in two human survivors.MethodsSerial blood samples were obtained from the only two survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T lymphocyte and B lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific IgM and IgG ELISA.ResultsAbsolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. Over 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B lymphocyte, activated B cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells.ConclusionWe describe for the first time longitudinal kinetic data on the activation status of human B and T cell populations during acute Nipah virus infection. While marked CD8 T cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

AB - BackgroundNipah virus (NiV) is one of ten potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in two human survivors.MethodsSerial blood samples were obtained from the only two survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T lymphocyte and B lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific IgM and IgG ELISA.ResultsAbsolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. Over 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B lymphocyte, activated B cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells.ConclusionWe describe for the first time longitudinal kinetic data on the activation status of human B and T cell populations during acute Nipah virus infection. While marked CD8 T cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

U2 - 10.1093/cid/ciz010

DO - 10.1093/cid/ciz010

M3 - Article

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

ER -