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Immune clearance of highly pathogenic SIV infection.

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Title: Immune clearance of highly pathogenic SIV infection.
Authors: Hansen, Scott G., Jr, Michael Piatak, Ventura, Abigail B., Hughes, Colette M., Gilbride, Roxanne M., Ford, Julia C., Oswald, Kelli, Shoemaker, Rebecca, Li, Yuan, Lewis, Matthew S., Gilliam, Awbrey N., Xu, Guangwu, Whizin, Nathan, Burwitz, Benjamin J., Planer, Shannon L., Turner, John M., Legasse, Alfred W., Axthelm, Michael K., Nelson, Jay A., Früh, Klaus
Source: Nature. 10/3/2013, Vol. 502 Issue 7469, p100-104. 5p.
Subjects: HIV, Simian immunodeficiency virus, Highly active antiretroviral therapy, Immune response, Cytomegalovirus diseases, Rhesus monkeys, T cells
Abstract: Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Immune clearance of highly pathogenic SIV infection.
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  Data: <searchLink fieldCode="AR" term="%22Hansen%2C+Scott+G%2E%22">Hansen, Scott G.</searchLink><br /><searchLink fieldCode="AR" term="%22Jr%2C+Michael+Piatak%22">Jr, Michael Piatak</searchLink><br /><searchLink fieldCode="AR" term="%22Ventura%2C+Abigail+B%2E%22">Ventura, Abigail B.</searchLink><br /><searchLink fieldCode="AR" term="%22Hughes%2C+Colette+M%2E%22">Hughes, Colette M.</searchLink><br /><searchLink fieldCode="AR" term="%22Gilbride%2C+Roxanne+M%2E%22">Gilbride, Roxanne M.</searchLink><br /><searchLink fieldCode="AR" term="%22Ford%2C+Julia+C%2E%22">Ford, Julia C.</searchLink><br /><searchLink fieldCode="AR" term="%22Oswald%2C+Kelli%22">Oswald, Kelli</searchLink><br /><searchLink fieldCode="AR" term="%22Shoemaker%2C+Rebecca%22">Shoemaker, Rebecca</searchLink><br /><searchLink fieldCode="AR" term="%22Li%2C+Yuan%22">Li, Yuan</searchLink><br /><searchLink fieldCode="AR" term="%22Lewis%2C+Matthew+S%2E%22">Lewis, Matthew S.</searchLink><br /><searchLink fieldCode="AR" term="%22Gilliam%2C+Awbrey+N%2E%22">Gilliam, Awbrey N.</searchLink><br /><searchLink fieldCode="AR" term="%22Xu%2C+Guangwu%22">Xu, Guangwu</searchLink><br /><searchLink fieldCode="AR" term="%22Whizin%2C+Nathan%22">Whizin, Nathan</searchLink><br /><searchLink fieldCode="AR" term="%22Burwitz%2C+Benjamin+J%2E%22">Burwitz, Benjamin J.</searchLink><br /><searchLink fieldCode="AR" term="%22Planer%2C+Shannon+L%2E%22">Planer, Shannon L.</searchLink><br /><searchLink fieldCode="AR" term="%22Turner%2C+John+M%2E%22">Turner, John M.</searchLink><br /><searchLink fieldCode="AR" term="%22Legasse%2C+Alfred+W%2E%22">Legasse, Alfred W.</searchLink><br /><searchLink fieldCode="AR" term="%22Axthelm%2C+Michael+K%2E%22">Axthelm, Michael K.</searchLink><br /><searchLink fieldCode="AR" term="%22Nelson%2C+Jay+A%2E%22">Nelson, Jay A.</searchLink><br /><searchLink fieldCode="AR" term="%22Früh%2C+Klaus%22">Früh, Klaus</searchLink>
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  Data: Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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