Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences

Abstract

Human immunodeficiency virus type 1 (HIV-1) sequences were generated from blood and from brain tissue obtained by stereotactic biopsy from six patients undergoing a diagnostic neurosurgical procedure. Proviral DNA was directly amplified by nested PCR, and 8 to 36 clones from each sample were sequenced. Phylogenetic analysis of intrapatient envelope V3-V5 region HIV-1 DNA sequence sets revealed that brain viral sequences were clustered relative to the blood viral sequences, suggestive of tissue-specific compartmentalization of the virus in four of the six cases. In the other two cases, the blood and brain virus sequences were intermingled in the phylogenetic analyses, suggesting trafficking of virus between the two tissues. Slide-based PCR-driven in situ hybridization of two of the patients' brain biopsy samples confirmed our interpretation of the intrapatient phylogenetic analyses. Interpatient V3 region brain-derived sequence distances were significantly less than blood-derived sequence distances. Relative to the tip of the loop, the set of brain-derived viral sequences had a tendency towards negative or neutral charge compared with the set of blood-derived viral sequences. Entropy calculations were used as a measure of the variability at each position in alignments of blood and brain viral sequences. A relatively conserved set of positions were found, with a significantly lower entropy in the brain

Viral Quasispecies Evolution

“…Virologists use the term viral quasispecies to mean distributions of nonidentical but related genomes subjected to a continuous pro-cess of genetic variation, competition, and selection and which act as a unit of selection (187,652). Strictly speaking, a viral quasispecies should be considered a single replicative unit in an infected cell (177,414,444,719). However, heterogeneous viral progeny from a single cell will invade neighboring cells in culture or from the same tissue or organ in vivo.…”

Evolutionary analysis of the dynamics of viral infectious disease

“…Phylodynamic methods have detected and measured the compartmentalization of viral lineages into specific tissues during chronic infection, which creates within-host subpopulations (so-called virodemes), which are analogous to the location-specific clusters of infection seen at higher scales. Highly distinct strains of HIV are found in the brains of patients with neurological illness 85,86 , suggesting that virus movement across the blood-brain barrier is not common and might be unidirectional. Finer genetic structure is apparent even among viruses from different brain regions, which seem to evolve at different rates 87 .…”

Molecular epidemiology of feline immunodeficiency virus in the domestic cat (Felis catus)

“…In HIV-1 infected individuals, it is suggested that compartmentalisation is a result of differential immune system pressures in the different tissue environments (Zhang et al, 2002;Kemal et al, 2003). The genitourinary tract, CNS, lymph node and lung have all been documented as HIV-1 compartments when compared to peripheral blood in the same individuals (Ball et al, 1994;Itescu et al, 1994;Korber et al, 1994;Byrn et al, 1997;Coombs et al, 1998). To date, an equivalent restriction of movement of FIV has not been published.…”