title: Longitudinal analysis of intra-host simian immunodeficiency virus recombination in varied tissues of the rhesus macaque model for neuroAIDS.
abstract: Human immunodeficiency virus intra-host recombination has never been studied in vivo both during early infection and throughout disease progression. The CD8-depleted rhesus macaque model of neuroAIDS was used to investigate the impact of recombination from early infection up to the onset of neuropathology in animals inoculated with a simian immunodeficiency virus (SIV) swarm. Several lymphoid and non-lymphoid tissues were collected longitudinally at 21 days post-infection (p.i.), 61 days p.i. and necropsy (75-118 days p.i.) from four macaques that developed SIV-encephalitis or meningitis, as well as from two animals euthanized at 21 days p.i. The number of recombinant sequences and breakpoints in different tissues and over time from each primate were compared. Breakpoint locations were mapped onto predicted RNA and protein secondary structures. Recombinants were found at each time point and in each primate as early as 21 days p.i. No association was found between recombination rates and specific tissue of origin. Several identical breakpoints were identified in sequences derived from different tissues in the same primate and among different primates. Breakpoints predominantly mapped to unpaired nucleotides or pseudoknots in RNA secondary structures, and proximal to glycosylation sites and cysteine residues in protein sequences, suggesting selective advantage in the emergence of specific recombinant sequences. Results indicate that recombinant sequences can become fixed very early after infection with a heterogeneous viral swarm. Features of RNA and protein secondary structure appear to play a role in driving the production of recombinants and their selection in the rapid disease model of neuroAIDS.
authors: BioInfoExperts LLC, Thibodaux, LA 70301, USA.
authors: Susanna L
authors: SL
authors: Lamers
authors: Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.|Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: David J
authors: DJ
authors: Nolan
authors: Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.|Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Samantha L
authors: SL
authors: Strickland
authors: Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.|Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Mattia
authors: M
authors: Prosperi
authors: Natural Selection Inc., San Diego, CA 92121, USA.
authors: Gary B
authors: GB
authors: Fogel
authors: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Maureen M
authors: MM
authors: Goodenow
authors: Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA.|Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Marco
authors: M
authors: Salemi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000150:complications / Q000821:virology*; D015658:HIV Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008587:Meningitis, Viral / Q000150:complications / Q000821:virology*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus
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