Efficient transmission and persistence of low-frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology.
Infection of CD8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (SIV)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and SIV-encephalitis (SIVE). The objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. Plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques euthanized at 21 days post-infection (p.i.), as well as longitudinal specimens and post-mortem tissues from four macaques followed throughout the infection. About 1300 gp120 viral sequences were obtained from the infecting SIVmac251 swarm and the macaques longitudinal and post-mortem samples. Phylogenetic and amino acid signature pattern analyses were carried out to assess frequency, transmission dynamics and persistence of specific viral clusters. Although no significant reduction in viral heterogeneity was found early in infection (21 days p.i.), transmission and replication of SIV variants was not entirely random. In particular, two distinct motifs under-represented (<4 %) in the infecting swarm were found at high frequencies (up to 14 %) in all six macaques as early as 21 days p.i. Moreover, a macrophage tropic variant not detected in the viral swarm (<0.3 %) was present at high frequency (29-100 %) in sequences derived from the brain of two macaques with meningitis or severe SIVE. This study demonstrates the highly efficient transmission and persistence in vivo of multiple low frequency SIVmac251 founder variants, characterized by specific gp120 motifs that may be linked to pathogenesis in the rapid-disease model of neuroAIDS.
Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.|Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Samantha L
SL
Strickland
Department of Zoology, University of Oxford, Oxford, UK.
Rebecca R
RR
Gray
BioInfoExperts, Thibodaux, LA, USA.
Susanna L
SL
Lamers
Department of Biology, Boston College, Chestnut Hill, MA, USA.
Tricia H
TH
Burdo
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Ellen
E
Huenink
Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.|Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
David J
DJ
Nolan
Department of Biology, Boston College, Chestnut Hill, MA, USA.
Brian
B
Nowlin
Tulane National Primate Research Center, Tulane University, Covington, LA, USA.
Xavier
X
Alvarez
Tulane National Primate Research Center, Tulane University, Covington, LA, USA.
Cecily C
CC
Midkiff
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Maureen M
MM
Goodenow
Department of Biology, Boston College, Chestnut Hill, MA, USA.
Kenneth
K
Williams
Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.|Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Marco
M
Salemi
D000818:Animals; D001921:Brain / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000821:virology*; D008168:Lung / Q000821:virology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000635:transmission* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification* / Q000472:pathogenicity*
D012367:RNA, Viral