title: Immune clearance of highly pathogenic SIV infection.
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.
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Hansen
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Ventura
authors.forename: Colette M
authors.initials: CM
authors.lastname: Hughes
authors.forename: Roxanne M
authors.initials: RM
authors.lastname: Gilbride
authors.forename: Julia C
authors.initials: JC
authors.lastname: Ford
authors.forename: Kelli
authors.initials: K
authors.lastname: Oswald
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shoemaker
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Lewis
authors.forename: Awbrey N
authors.initials: AN
authors.lastname: Gilliam
authors.forename: Guangwu
authors.initials: G
authors.lastname: Xu
authors.forename: Nathan
authors.initials: N
authors.lastname: Whizin
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Planer
authors.forename: John M
authors.initials: JM
authors.lastname: Turner
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Legasse
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.forename: Klaus
authors.initials: K
authors.lastname: Früh
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
mesh_terms: D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology
chemical_list: D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated
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