Format

Send to

Choose Destination
J Gen Virol. 2012 May;93(Pt 5):925-38. doi: 10.1099/vir.0.039586-0. Epub 2012 Feb 1.

Efficient transmission and persistence of low-frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology.

Author information

1
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.

Abstract

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.

PMID:
22302881
PMCID:
PMC3541805
DOI:
10.1099/vir.0.039586-0
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substance, Secondary source ID, Grant support

Publication type

MeSH terms

Substance

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Ingenta plc Icon for PubMed Central
Loading ...
Support Center