Novel strategy to adapt simian-human immunodeficiency virus e1 carrying env from an rv144 volunteer to rhesus macaques: Coreceptor switch and final recovery of a pathogenic virus with exclusive r5 tropism

Hanna B. Scinto, Sandeep Gupta, Swati Thorat, Muhammad M. Mukhtar, Anthony Griffiths, Jennifer Delgado, Elizabeth Plake, Hemant K. Vyas, Amanda Strickland, Siddappa N. Byrareddy, David C. Montefiori, Celia LaBranche, Ranajit Pal, Jim Treece, Sharon Orndorff, Maria Grazia Ferrari, Deborah Weiss, Agnes Laurence Chenine, Robert McLinden, Nelson MichaelJerome H. Kim, Merlin L. Robb, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Ruth M. Ruprecht

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The phase III RV144 human immunodeficiency virus (HIV) vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing the HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clade A/E (CRF01_AE) predominate; in such viruses, env originates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carrying env isolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-B sites, thus resembling HIV LTRs. We devised a novel strategy to adapt the parental infectious molecular clone (IMC), R5 SHIV-E1, to rhesus macaques: the simultaneous depletion of B and CD8 cells followed by the intramuscular inoculation of proviral DNA and repeated administrations of cell-free virus. High-level viremia and CD4 T-cell depletion ensued. Passage 3 virus unexpectedly caused acute, irreversible CD4 T-cell loss; the partially adapted SHIV had become dual tropic. Virus and IMCs with exclusive R5 tropism were reisolated from earlier passages, combined, and used to complete adaptation through additional macaques. The final isolate, SHIV-E1p5, remained solely R5 tropic. It had a tier 2 neutralization phenotype, was mucosally transmissible, and was pathogenic. Deep sequencing revealed 99% Env amino acid sequence conservation; X4-only and dual-tropic strains had evolved independently from an early branch of parental SHIV-E1. To conclude, our primate model data reveal that SHIV-E1p5 recapitulates important aspects of HIV transmission and pathobiology in humans.

Original languageEnglish (US)
Article numbere02222-17
JournalJournal of Virology
Volume92
Issue number14
DOIs
StatePublished - Jul 1 2018
Externally publishedYes

Fingerprint

Simian Immunodeficiency Virus
tropisms
Tropism
Human immunodeficiency virus
Macaca mulatta
volunteers
Volunteers
HIV
Viruses
viruses
tropics
terminal repeat sequences
Thailand
HIV Long Terminal Repeat
T-lymphocytes
T-Lymphocytes
High-Throughput Nucleotide Sequencing
Terminal Repeat Sequences
Viremia
Macaca

Keywords

  • Adaptation
  • Coreceptor switch
  • CRF01_AE
  • HIV
  • HIV
  • Rhesus macaques
  • RV144 trial
  • SHIV-E

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Novel strategy to adapt simian-human immunodeficiency virus e1 carrying env from an rv144 volunteer to rhesus macaques : Coreceptor switch and final recovery of a pathogenic virus with exclusive r5 tropism. / Scinto, Hanna B.; Gupta, Sandeep; Thorat, Swati; Mukhtar, Muhammad M.; Griffiths, Anthony; Delgado, Jennifer; Plake, Elizabeth; Vyas, Hemant K.; Strickland, Amanda; Byrareddy, Siddappa N.; Montefiori, David C.; LaBranche, Celia; Pal, Ranajit; Treece, Jim; Orndorff, Sharon; Ferrari, Maria Grazia; Weiss, Deborah; Chenine, Agnes Laurence; McLinden, Robert; Michael, Nelson; Kim, Jerome H.; Robb, Merlin L.; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayaphan, Sorachai; Ruprecht, Ruth M.

In: Journal of Virology, Vol. 92, No. 14, e02222-17, 01.07.2018.

Research output: Contribution to journalArticle

Scinto, HB, Gupta, S, Thorat, S, Mukhtar, MM, Griffiths, A, Delgado, J, Plake, E, Vyas, HK, Strickland, A, Byrareddy, SN, Montefiori, DC, LaBranche, C, Pal, R, Treece, J, Orndorff, S, Ferrari, MG, Weiss, D, Chenine, AL, McLinden, R, Michael, N, Kim, JH, Robb, ML, Rerks-Ngarm, S, Pitisuttithum, P, Nitayaphan, S & Ruprecht, RM 2018, 'Novel strategy to adapt simian-human immunodeficiency virus e1 carrying env from an rv144 volunteer to rhesus macaques: Coreceptor switch and final recovery of a pathogenic virus with exclusive r5 tropism', Journal of Virology, vol. 92, no. 14, e02222-17. https://doi.org/10.1128/JVI.02222-17
Scinto, Hanna B. ; Gupta, Sandeep ; Thorat, Swati ; Mukhtar, Muhammad M. ; Griffiths, Anthony ; Delgado, Jennifer ; Plake, Elizabeth ; Vyas, Hemant K. ; Strickland, Amanda ; Byrareddy, Siddappa N. ; Montefiori, David C. ; LaBranche, Celia ; Pal, Ranajit ; Treece, Jim ; Orndorff, Sharon ; Ferrari, Maria Grazia ; Weiss, Deborah ; Chenine, Agnes Laurence ; McLinden, Robert ; Michael, Nelson ; Kim, Jerome H. ; Robb, Merlin L. ; Rerks-Ngarm, Supachai ; Pitisuttithum, Punnee ; Nitayaphan, Sorachai ; Ruprecht, Ruth M. / Novel strategy to adapt simian-human immunodeficiency virus e1 carrying env from an rv144 volunteer to rhesus macaques : Coreceptor switch and final recovery of a pathogenic virus with exclusive r5 tropism. In: Journal of Virology. 2018 ; Vol. 92, No. 14.
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AU - Gupta, Sandeep

AU - Thorat, Swati

AU - Mukhtar, Muhammad M.

AU - Griffiths, Anthony

AU - Delgado, Jennifer

AU - Plake, Elizabeth

AU - Vyas, Hemant K.

AU - Strickland, Amanda

AU - Byrareddy, Siddappa N.

AU - Montefiori, David C.

AU - LaBranche, Celia

AU - Pal, Ranajit

AU - Treece, Jim

AU - Orndorff, Sharon

AU - Ferrari, Maria Grazia

AU - Weiss, Deborah

AU - Chenine, Agnes Laurence

AU - McLinden, Robert

AU - Michael, Nelson

AU - Kim, Jerome H.

AU - Robb, Merlin L.

AU - Rerks-Ngarm, Supachai

AU - Pitisuttithum, Punnee

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