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Pathogenesis and Immunity

Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1

Gülşen Özkaya Şahin, Birgitta Holmgren, Zacarias da Silva, Jens Nielsen, Salma Nowroozalizadeh, Joakim Esbjörnsson, Fredrik Månsson, Sören Andersson, Hans Norrgren, Peter Aaby, Marianne Jansson, Eva Maria Fenyö
Gülşen Özkaya Şahin
aDepartment of Laboratory Medicine Lund, Lund University, Lund, Sweden
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Birgitta Holmgren
aDepartment of Laboratory Medicine Lund, Lund University, Lund, Sweden
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Zacarias da Silva
bBandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau
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Jens Nielsen
cStatens Serum Institute, Copenhagen, Denmark
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Salma Nowroozalizadeh
dDepartment of Virology, Swedish Institute for Infectious Disease Control, Stockholm, Sweden
eDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Joakim Esbjörnsson
fDepartment of Experimental Medical Science, Lund University, Lund, Sweden
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Fredrik Månsson
gInfectious Diseases Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden
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Sören Andersson
dDepartment of Virology, Swedish Institute for Infectious Disease Control, Stockholm, Sweden
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Hans Norrgren
hDivision of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden
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Peter Aaby
bBandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau
cStatens Serum Institute, Copenhagen, Denmark
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Marianne Jansson
aDepartment of Laboratory Medicine Lund, Lund University, Lund, Sweden
eDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Eva Maria Fenyö
aDepartment of Laboratory Medicine Lund, Lund University, Lund, Sweden
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DOI: 10.1128/JVI.06315-11
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ABSTRACT

HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent and also broader than intratype NAc in HIV-1 plasma. This indicates that HIV-2-infected individuals display potent type-specific neutralizing antibodies, whereas such strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the viral load of HIV-1 but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation dependent than in HIV-2 infection, where plasma viral loads typically are at least 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections was, instead, of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2-infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses.

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Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1
Gülşen Özkaya Şahin, Birgitta Holmgren, Zacarias da Silva, Jens Nielsen, Salma Nowroozalizadeh, Joakim Esbjörnsson, Fredrik Månsson, Sören Andersson, Hans Norrgren, Peter Aaby, Marianne Jansson, Eva Maria Fenyö
Journal of Virology Dec 2011, 86 (2) 961-971; DOI: 10.1128/JVI.06315-11

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Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1
Gülşen Özkaya Şahin, Birgitta Holmgren, Zacarias da Silva, Jens Nielsen, Salma Nowroozalizadeh, Joakim Esbjörnsson, Fredrik Månsson, Sören Andersson, Hans Norrgren, Peter Aaby, Marianne Jansson, Eva Maria Fenyö
Journal of Virology Dec 2011, 86 (2) 961-971; DOI: 10.1128/JVI.06315-11
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