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Transmitted/founder simian immunodeficiency virus envelope sequences in vesicular stomatitis and Semliki forest virus vector immunized rhesus macaques.
- Source :
-
PloS one [PLoS One] 2014 Oct 31; Vol. 9 (10), pp. e109678. Date of Electronic Publication: 2014 Oct 31 (Print Publication: 2014). - Publication Year :
- 2014
-
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.
- Subjects :
- Animals
Gene Products, env genetics
Gene Products, env immunology
Gene Products, gag genetics
Genetic Vectors
Granulocyte-Macrophage Colony-Stimulating Factor immunology
Immunization
Macaca mulatta immunology
Molecular Sequence Data
SAIDS Vaccines immunology
Semliki forest virus genetics
Semliki forest virus immunology
Simian Acquired Immunodeficiency Syndrome transmission
Simian Immunodeficiency Virus genetics
Simian Immunodeficiency Virus immunology
Vesicular Stomatitis virology
Viral Envelope Proteins immunology
Viral Load
Macaca mulatta virology
Phylogeny
Simian Acquired Immunodeficiency Syndrome virology
Viral Envelope Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25360552
- Full Text :
- https://doi.org/10.1371/journal.pone.0109678