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.

Autor:	Scinto HB; Texas Biomedical Research Institute, San Antonio, Texas, USA.; UT Health San Antonio, San Antonio, Texas, USA., Gupta S; Texas Biomedical Research Institute, San Antonio, Texas, USA., Thorat S; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Mukhtar MM; Texas Biomedical Research Institute, San Antonio, Texas, USA., Griffiths A; Texas Biomedical Research Institute, San Antonio, Texas, USA., Delgado J; Texas Biomedical Research Institute, San Antonio, Texas, USA., Plake E; Texas Biomedical Research Institute, San Antonio, Texas, USA., Vyas HK; Texas Biomedical Research Institute, San Antonio, Texas, USA., Strickland A; Texas Biomedical Research Institute, San Antonio, Texas, USA., Byrareddy SN; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Montefiori DC; Duke University Medical Center, Durham, North Carolina, USA., LaBranche C; Duke University Medical Center, Durham, North Carolina, USA., Pal R; Advanced Biosciences Laboratories Inc., Rockville, Maryland, USA., Treece J; Advanced Biosciences Laboratories Inc., Rockville, Maryland, USA., Orndorff S; Advanced Biosciences Laboratories Inc., Rockville, Maryland, USA., Ferrari MG; Advanced Biosciences Laboratories Inc., Rockville, Maryland, USA., Weiss D; Advanced Biosciences Laboratories Inc., Rockville, Maryland, USA., Chenine AL; Henry M. Jackson Foundation, Bethesda, Maryland, USA., McLinden R; Henry M. Jackson Foundation, Bethesda, Maryland, USA., Michael N; Henry M. Jackson Foundation, Bethesda, Maryland, USA., Kim JH; Henry M. Jackson Foundation, Bethesda, Maryland, USA.; International Vaccine Institute, Seoul, South Korea., Robb ML; Henry M. Jackson Foundation, Bethesda, Maryland, USA., Rerks-Ngarm S; Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand., Pitisuttithum P; Mahidol University, Bangkok, Thailand., Nitayaphan S; Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand., Ruprecht RM; Texas Biomedical Research Institute, San Antonio, Texas, USA rrupecht@txbiomd.org.; UT Health San Antonio, San Antonio, Texas, USA.; Dana-Farber Cancer Institute, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2018 Jun 29; Vol. 92 (14). Date of Electronic Publication: 2018 Jun 29 (Print Publication: 2018).
DOI:	10.1128/JVI.02222-17
Abstrakt:	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-κB 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. IMPORTANCE Understanding the protective principles that lead to a safe, effective vaccine against HIV in nonhuman primate (NHP) models requires test viruses that allow the evaluation of anti-HIV envelope responses. Reduced HIV acquisition risk in RV144 has been linked to nonneutralizing IgG antibodies with a range of effector activities. Definitive experiments to decipher the mechanisms of the partial protection observed in RV144 require passive-immunization studies in NHPs with a relevant test virus. We have generated such a virus by inserting env from an RV144 placebo recipient into a SHIV backbone with HIV-like LTRs. The final SHIV-E1p5 isolate, grown in rhesus monkey peripheral blood mononuclear cells, was mucosally transmissible and pathogenic. Earlier SHIV-E passages showed a coreceptor switch, again mimicking HIV biology in humans. Thus, our series of SHIV-E strains mirrors HIV transmission and disease progression in humans. SHIV-E1p5 represents a biologically relevant tool to assess prevention strategies. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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