Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients

M. Nevot; C. Boesecke; M. Parera; C. Andrés; S. Franco; B. Revollo; P. Ingiliz; C. Tural; B. Clotet; J. K. Rockstroh; M. A. Martinez

doi:10.1111/jvh.12254

Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients

M. Nevot, C. Boesecke, M. Parera, C. Andrés, S. Franco, B. Revollo, P. Ingiliz, C. Tural, B. Clotet, J. K. Rockstroh, M. A. Martinez

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El nombre creixent de casos d'infeccions agudes per hepatitis C (AHC) entre homes amb VIH-1 que tenen relacions sexuals amb altres homes en els darrers 10 anys ha promogut la cerca de predictors de l'eliminació de l'AHC així com les xarxes epidemiològiques de transmissió viral. Hem caracteritzat la diversitat i eficiència catalítica de la proteasa NS3/4A del VHC en pacients coinfectats amb VIH-1 que tenen relacions sexuals amb altres homes (MSM) durant els darrers 10 anys. S'han estudiat mostres de plasma obtingudes en el diagnòstic d'hepatitis C per HCV de 18 MSM infectats pel VIH i coinfectats amb AHC. També s'ha investigat cinc pacients monoinfectats amb AHC. Es va analitzar una mitjana de 39 clons de cada mostra. L'eficiència catalítica de la quasiespècie dominant (és a dir, la més abundant) de cada quasiespècie també es va assajar per l'escissió de la proteïna antiviral mitocondrial (MAVS). L'anàlisi filogenètica ha identificat dos grups de pacients amb virus altament relacionats, suggerint una font comuna d'infecció pel VHC. Cap dels 18 MSM infectats pel VIH espontàniament va eliminar el VHC, tot i que un 78% dels pacients tractats van aconseguir una resposta virològica sostinguda després del tractament precoç amb interferó pegilat (PEGIFN) més ribavirina (RBV). La relació de mutacions sinònimes/no sinònimes (ds/dn), un marcador de pressió selectiva, va ser superior en els pacients d'AHC comparats amb 26 homes infectats pel VIH-1 amb hepatitis crònica C (CHC) del genotip 1a (P < 0.0001). Les proteases NS3/4A de pacients AHC també van exhibir una eficiència catalítica superior en comparació amb els pacients CHC (P < 0.0001). No es va trobar cap diferència quan es va comparar la relació de mutacions sinònimes/no sinònimes i l'eficiència catalítica de les proteases NS3/4A dels pacients AHC infectats per VIH amb els pacients monoinfectats d'AHC. La presència de xarxes epidemiològiques de transmissió del VHC entre homes seropositius al VIH-1 s'ha confirmat. A més, es va demostrar una diversitat genètica substancial en l'AHC. L'eficiència catalítica de la proteasa NS3/4A que talla MAVS pot estar associada amb la transmissió viral i resposta al tractament pegIFN/RBV. © 2014 John Wiley & Sons Ltd.

Idioma original	Anglès
Revista	Journal of Viral Hepatitis
Volum	21
Número	6
DOIs	https://doi.org/10.1111/jvh.12254
Estat de la publicació	Publicada - 1 de gen. 2014

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10.1111/jvh.12254

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https://www.scopus.com/pages/publications/84901004239

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@article{853eb338bce14ecba0a371ed62db05f6,

title = "Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients",

abstract = "The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78\% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment. {\textcopyright} 2014 John Wiley \& Sons Ltd.",

keywords = "acute infection, catalytic efficiency, HCV, HIV co-infection, protease, quasispecies",

author = "M. Nevot and C. Boesecke and M. Parera and C. Andr{\'e}s and S. Franco and B. Revollo and P. Ingiliz and C. Tural and B. Clotet and Rockstroh, \{J. K.\} and Martinez, \{M. A.\}",

year = "2014",

month = jan,

day = "1",

doi = "10.1111/jvh.12254",

language = "English",

volume = "21",

journal = "Journal of Viral Hepatitis",

issn = "1352-0504",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

TY - JOUR

T1 - Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients

AU - Nevot, M.

AU - Boesecke, C.

AU - Parera, M.

AU - Andrés, C.

AU - Franco, S.

AU - Revollo, B.

AU - Ingiliz, P.

AU - Tural, C.

AU - Clotet, B.

AU - Rockstroh, J. K.

AU - Martinez, M. A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment. © 2014 John Wiley & Sons Ltd.

AB - The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment. © 2014 John Wiley & Sons Ltd.

KW - acute infection

KW - catalytic efficiency

KW - HCV

KW - HIV co-infection

KW - protease

KW - quasispecies

UR - https://www.scopus.com/pages/publications/84901004239

U2 - 10.1111/jvh.12254

DO - 10.1111/jvh.12254

M3 - Article

SN - 1352-0504

VL - 21

JO - Journal of Viral Hepatitis

JF - Journal of Viral Hepatitis

IS - 6

ER -

Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients

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