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Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients

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http://www.ingentaconnect.com/content/bsc/jvh/2011/00000018/00000010/art00019

Cellular immune responses and occult infection in seronegative heterosexual

partners of chronic hepatitis C patients Authors: Roque-Cuéllar, M.

C.1; Sánchez, B.2; García-Lozano, J. R.2; Praena-Fernández, J. M.3;

Núñez-Roldán, A.2; Aguilar-Reina, J.1Source: Journal of Viral Hepatitis,

Volume 18, Number 10, 1 October 2011 , pp. e541-e549(9)Publisher:

Wiley-Blackwell Abstract:Summary.  It is unknown whether hepatitis C virus

(HCV)-specific cellular immune responses can develop in seronegative sexual

partners of chronically HCV-infected patients and whether they have occult

infection. Thirty-one heterosexual partners of patients with chronic HCV were

studied, fifteen of them with HCV transmission risks. Ten healthy individuals

and 17 anti-HCV seropositive patients, without viremia, were used as controls.

Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry

against six HCV peptides, situated within the nonstructural (NS) proteins NS3,

NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or

interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a

higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124

(P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and

CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and

NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated

IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and

NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks

(sexual, professional and familial altogether) than in those without risks. RNA

was extracted from peripheral blood mononuclear cells (PBMC), and detection of

HCV-RNA positive and replicative (negative) strands was performed by

strand-specific real-time PCR. In four sexual partners, the presence of positive

and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an

HCV-specific cellular immune response as well as occult HCV infection in

seronegative and aviremic sexual partners of chronically HCV-infected patients.

Document Type: Research article DOI:

10.1111/j.1365-2893.2011.01464.xAffiliations:1:

Grupo Sección de Hepatología, Servicio de Aparato Digestivo Hospital

Universitario Virgen del Rocío de Sevilla2:

Servicio de Inmunología, Hospital Universitario Virgen del Rocío de Sevilla3:

Unidad de Metodología y Evaluación de la Investigación. Fundación Pública

Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI),

IBIS. Hospital Universitario Virgen del Rocío de Sevilla, SpainPublication

date: 2011-10-01

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http://www.ingentaconnect.com/content/bsc/jvh/2011/00000018/00000010/art00019

Cellular immune responses and occult infection in seronegative heterosexual

partners of chronic hepatitis C patients Authors: Roque-Cuéllar, M.

C.1; Sánchez, B.2; García-Lozano, J. R.2; Praena-Fernández, J. M.3;

Núñez-Roldán, A.2; Aguilar-Reina, J.1Source: Journal of Viral Hepatitis,

Volume 18, Number 10, 1 October 2011 , pp. e541-e549(9)Publisher:

Wiley-Blackwell Abstract:Summary.  It is unknown whether hepatitis C virus

(HCV)-specific cellular immune responses can develop in seronegative sexual

partners of chronically HCV-infected patients and whether they have occult

infection. Thirty-one heterosexual partners of patients with chronic HCV were

studied, fifteen of them with HCV transmission risks. Ten healthy individuals

and 17 anti-HCV seropositive patients, without viremia, were used as controls.

Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry

against six HCV peptides, situated within the nonstructural (NS) proteins NS3,

NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or

interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a

higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124

(P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and

CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and

NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated

IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and

NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks

(sexual, professional and familial altogether) than in those without risks. RNA

was extracted from peripheral blood mononuclear cells (PBMC), and detection of

HCV-RNA positive and replicative (negative) strands was performed by

strand-specific real-time PCR. In four sexual partners, the presence of positive

and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an

HCV-specific cellular immune response as well as occult HCV infection in

seronegative and aviremic sexual partners of chronically HCV-infected patients.

Document Type: Research article DOI:

10.1111/j.1365-2893.2011.01464.xAffiliations:1:

Grupo Sección de Hepatología, Servicio de Aparato Digestivo Hospital

Universitario Virgen del Rocío de Sevilla2:

Servicio de Inmunología, Hospital Universitario Virgen del Rocío de Sevilla3:

Unidad de Metodología y Evaluación de la Investigación. Fundación Pública

Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI),

IBIS. Hospital Universitario Virgen del Rocío de Sevilla, SpainPublication

date: 2011-10-01

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