title: Transmitted/founder simian immunodeficiency virus envelope sequences in vesicular stomatitis and Semliki forest virus vector immunized rhesus macaques.
abstract: Identification of transmitted/founder simian immunodeficiency virus (SIV) envelope sequences responsible for infection may prove critical for understanding HIV/SIV mucosal transmission. We used single genome amplification and phylogenetic analyses to characterize transmitted/founder SIVs both in the inoculum and in immunized-infected rhesus monkeys. Single genome amplification of the SIVsmE660 inoculum revealed a maximum diversity of 1.4%. We also noted that the consensus sequence of the challenge stock differed from the vaccine construct in 10 amino acids including 3 changes in the V4 loop. Viral env was prepared from rhesus plasma in 3 groups of 6 immunized with vesicular stomatitis virus (VSV) vectors and boosted with Semliki forest virus (SFV) replicons expressing (a) SIVsmE660 gag-env (b) SIVsmE660 gag-env plus rhesus GM-CSF and (c) control influenza hemagglutinin protein. Macaques were immunized twice with VSV-vectors and once with SFV vector and challenged intrarectally with 4000 TCID50. Single genome amplification characterized the infections of 2 unprotected animals in the gag-env immunized group, both of which had reduced acute plasma viral loads that ended as transient infections indicating partial immune control. Four of 6 rhesus were infected in the gag-env + GM-CSF group which demonstrated that GM-CSF abrogated protection. All 6 animals from the control group were infected having high plasma viral loads. We obtained 246 full-length envelope sequences from SIVsmE660 infected macaques at the peak of infection and determined the number of transmitted/founder variants per animal. Our analysis found that 2 of 2 gag-env vaccinated but infected macaques exhibited single but distinct virus envelope lineages whereas rhesus vaccinated with gag-env-GM-CSF or HA control exhibited both single and multiple env lineages. Because there were only 2 infected animals in the gag-env vaccinated rhesus compared to 10 infected rhesus in the other 2 groups, the significance of finding single env variants in the gag-env vaccinated group could not be established.
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: Ratish
authors.initials: R
authors.lastname: Gambhira
authors.affiliation: AIDS and Cancer Virus Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.affiliation: Department of Pathology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: John B
authors.initials: JB
authors.lastname: Schell
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Hunter
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Dufour
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Haili
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pathology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
authors.affiliation: Department of Pathology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Nina
authors.initials: N
authors.lastname: Rose
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
mesh_terms: D000818:Animals; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D007114:Immunization; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D018449:SAIDS Vaccines / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054243:Vesicular Stomatitis / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D019562:Viral Load
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor