Immune clearance of highly pathogenic SIV infection

Scott Hansen, Michael Piatak Jr, Abigail B. Ventura, Colette M. Hughes, Roxanne M. Gilbride, Julia C. Ford, Kelli Oswald, Rebecca Shoemaker, Yuan Li, Matthew S. Lewis, Awbrey N. Gilliam, Guangwu Xu, Nathan Whizin, Benjamin Burwitz, Shannon L. Planer, John M. Turner, Alfred W. Legasse, Michael Axthelm, Jay Nelson, Klaus FruehJonah Sacha, Jacob Estes, Brandon F. Keele, Paul T. Edlefsen, Jeffrey D. Lifson, Louis Picker

Research output: Contribution to journalArticle

332 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)100-104
Number of pages5
JournalNature
Volume502
Issue number7469
DOIs
StatePublished - 2013

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HIV
Infection
Macaca mulatta
Cytomegalovirus
T-Lymphocytes
Satellite Viruses
Simian Immunodeficiency Virus
Polymerase Chain Reaction
Adoptive Transfer
Virus Diseases
Infection Control
Coculture Techniques
Reverse Transcription
Vaccines
Proteins
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Hansen, S., Jr, M. P., Ventura, A. B., Hughes, C. M., Gilbride, R. M., Ford, J. C., ... Picker, L. (2013). Immune clearance of highly pathogenic SIV infection. Nature, 502(7469), 100-104. https://doi.org/10.1038/nature12519

Immune clearance of highly pathogenic SIV infection. / Hansen, Scott; 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; Planer, Shannon L.; Turner, John M.; Legasse, Alfred W.; Axthelm, Michael; Nelson, Jay; Frueh, Klaus; Sacha, Jonah; Estes, Jacob; Keele, Brandon F.; Edlefsen, Paul T.; Lifson, Jeffrey D.; Picker, Louis.

In: Nature, Vol. 502, No. 7469, 2013, p. 100-104.

Research output: Contribution to journalArticle

Hansen, S, Jr, MP, Ventura, AB, Hughes, CM, Gilbride, RM, Ford, JC, Oswald, K, Shoemaker, R, Li, Y, Lewis, MS, Gilliam, AN, Xu, G, Whizin, N, Burwitz, B, Planer, SL, Turner, JM, Legasse, AW, Axthelm, M, Nelson, J, Frueh, K, Sacha, J, Estes, J, Keele, BF, Edlefsen, PT, Lifson, JD & Picker, L 2013, 'Immune clearance of highly pathogenic SIV infection', Nature, vol. 502, no. 7469, pp. 100-104. https://doi.org/10.1038/nature12519
Hansen S, Jr MP, Ventura AB, Hughes CM, Gilbride RM, Ford JC et al. Immune clearance of highly pathogenic SIV infection. Nature. 2013;502(7469):100-104. https://doi.org/10.1038/nature12519
Hansen, Scott ; 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 ; Planer, Shannon L. ; Turner, John M. ; Legasse, Alfred W. ; Axthelm, Michael ; Nelson, Jay ; Frueh, Klaus ; Sacha, Jonah ; Estes, Jacob ; Keele, Brandon F. ; Edlefsen, Paul T. ; Lifson, Jeffrey D. ; Picker, Louis. / Immune clearance of highly pathogenic SIV infection. In: Nature. 2013 ; Vol. 502, No. 7469. pp. 100-104.
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