Molecularly tagged simian immunodeficiency virus SIVmac239 synthetic swarm for tracking independent infection events

Gregory Q. Del Prete, Haesun Park, Christine M. Fennessey, Carolyn Reid, Leslie Lipkey, Laura Newman, Kelli Oswald, Christoph Kahl, Michael Piatak, Octavio A. Quiñones, W. Gregory Alvord, Jeremy Smedley, Jacob Estes, Jeffrey D. Lifson, Louis Picker, Brandon F. Keele

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Following mucosal human immunodeficiency virus type 1 transmission, systemic infection is established by one or only a few viral variants. Modeling single-variant, mucosal transmission in nonhuman primates using limiting-dose inoculations with a diverse simian immunodeficiency virus isolate stock may increase variability between animals since individual variants within the stock may have substantial functional differences. To decrease variability between animals while retaining the ability to enumerate transmitted/founder variants by sequence analysis, we modified the SIVmac239 clone to generate 10 unique clones that differ by two or three synonymous mutations (molecular tags). Transfection- and infection-derived virus stocks containing all 10 variants showed limited phenotypic differences in 9 of the 10 clones. Twenty-nine rhesus macaques were challenged intrarectally or intravenously with either a single dose or repeated, limiting doses of either stock. The proportion of each variant within each inoculum and in plasma from infected animals was determined by using a novel real-time single-genome amplification assay. Each animal was infected with one to five variants, the number correlating with the dose. Longitudinal sequence analysis revealed that the molecular tags are highly stable with no reversion to the parental sequence detected in >2 years of follow-up. Overall, the viral stocks are functional and mucosally transmissible and the number of variants is conveniently discernible by sequence analysis of a small amplicon. This approach should be useful for tracking individual infection events in preclinical vaccine evaluations, long-term viral reservoir establishment/clearance research, and transmission/early-event studies.

Original languageEnglish (US)
Pages (from-to)8077-8090
Number of pages14
JournalJournal of Virology
Volume88
Issue number14
DOIs
StatePublished - 2014

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
swarms
Sequence Analysis
sequence analysis
Clone Cells
clones
dosage
Infection
infection
animals
Infectious Disease Transmission
Virus Diseases
transfection
Human immunodeficiency virus 1
Macaca mulatta
Primates
Transfection
HIV-1
inoculum

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Molecularly tagged simian immunodeficiency virus SIVmac239 synthetic swarm for tracking independent infection events. / Del Prete, Gregory Q.; Park, Haesun; Fennessey, Christine M.; Reid, Carolyn; Lipkey, Leslie; Newman, Laura; Oswald, Kelli; Kahl, Christoph; Piatak, Michael; Quiñones, Octavio A.; Gregory Alvord, W.; Smedley, Jeremy; Estes, Jacob; Lifson, Jeffrey D.; Picker, Louis; Keele, Brandon F.

In: Journal of Virology, Vol. 88, No. 14, 2014, p. 8077-8090.

Research output: Contribution to journalArticle

Del Prete, GQ, Park, H, Fennessey, CM, Reid, C, Lipkey, L, Newman, L, Oswald, K, Kahl, C, Piatak, M, Quiñones, OA, Gregory Alvord, W, Smedley, J, Estes, J, Lifson, JD, Picker, L & Keele, BF 2014, 'Molecularly tagged simian immunodeficiency virus SIVmac239 synthetic swarm for tracking independent infection events', Journal of Virology, vol. 88, no. 14, pp. 8077-8090. https://doi.org/10.1128/JVI.01026-14
Del Prete, Gregory Q. ; Park, Haesun ; Fennessey, Christine M. ; Reid, Carolyn ; Lipkey, Leslie ; Newman, Laura ; Oswald, Kelli ; Kahl, Christoph ; Piatak, Michael ; Quiñones, Octavio A. ; Gregory Alvord, W. ; Smedley, Jeremy ; Estes, Jacob ; Lifson, Jeffrey D. ; Picker, Louis ; Keele, Brandon F. / Molecularly tagged simian immunodeficiency virus SIVmac239 synthetic swarm for tracking independent infection events. In: Journal of Virology. 2014 ; Vol. 88, No. 14. pp. 8077-8090.
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