Independent Evolution of HIV Type 1 in Different Brain Regions

Abstract

HIV-1-associated brain pathology exhibits regional variability and we therefore studied the genetic differences in the V1-V5 domains of the HIV env gene in up to four regions of brain (frontal lobe, basal ganglia, medial temporal lobe, and nonmedial temporal lobe) from three patients. We found that in each separate brain region HIV-1 forms different quasispecies and that there is little gene flow among these regions. In further support of brain region-specific evolution of HIV-1, we analyzed amino acid signatures in these clones. In addition to known amino acid signatures associated with macrophage tropism and the lack of syncytium formation, we found 15 majority amino acid signature patterns from the V1-V5 env sequences associated with the neuroanatomical regions analyzed from the three individuals. Furthermore, on average, intrabrain genetic distances for the HIV-1 env were estimated to be much smaller than genetic distances between brain regions. Specific strains of HIV-1 may be neurotropic or neuroinvasive (replication preference in brain tissue) and may contribute to pathology, cognitive loss, and neuropsychiatric disease.

Molecular study of the quasispecies evolution of a typical pigeon paramyxovirus type 1 after serial passages in pigeons by contact

“…One of the main points of discussion is the way subpopulations should be described. Whereas Domingo and colleagues (Domingo et al , 1996(Domingo et al , , 2003Domingo & Holland, 1997;RuizJarabo et al , 2000RuizJarabo et al , , 2002 consider each mutation to define subpopulations, Smith et al (1997) recommend limiting the definition of the subpopulations to the ................................................................................................................................. ino.1.b Figure 2. Alignment of clone sequences obtained for the HN gene of the 99299 strain inoculum.…”

“…Differences in the quasispecies complexity according to the organ were observed for other viruses (Laskus et al , 2000;Rü ster et al , 2001). Depending on the cell type, some mechanisms might occur more or less rapidly after infection, modifying the concentration of ions or other oligo-elements and so, disrupting the working of the viral polymerase (Shapshak et al , 1999). The insertions in the P gene editing site on the viral genomic strand might be due to the stuttering of the polymerase by a similar mechanism to that responsible for the appearance of mRNA coding for the V and W proteins (Steward et al , 1993).…”

“…Depending on the cell type, some mechanisms might occur more or less rapidly after infection, modifying the concentration of ions or other oligo-elements and so, disrupting the working of the viral polymerase (Shapshak et al , 1999). The insertions in the P gene editing site on the viral genomic strand might be due to the stuttering of the polymerase by a similar mechanism to that responsible for the appearance of mRNA coding for the V and W proteins (Steward et al , 1993). These insertions might have an influence on the level of V and W proteins produced in the infected cells with consequences on pathogenesis, since the V protein is believed to play a role in inhibiting the host interferon response (Kato et al , 1997;Delenda et al , 1998;Komatsu et al , 2004).…”

Genetic drift and within-host metapopulation dynamics of HIV-1 infection

“…Although spatial models have been applied to the question of HIV population structure, these models have been of the ''island'' type, which does not allow for extinction of subpopulations, and where dissemination of virus is assumed to occur only between extant subpopulations, such as between different parts of the brain (63) and between the plasma and cerebrospinal fluid. ** Although this may be a reasonable assumption when looking at large-scale population structure (as large subpopulations are unlikely to go extinct), or when looking at infection of glial cells in the brain (which undergo slow turnover), turnover of productively infected T cells in solid lymphoid tissue is high because of local exhaustion of target cells and͞or to the infiltration of HIV-specific cytotoxic T cells (37,38) and with low levels of mixing will lead to extinction of foci of infection.…”

International NeuroAIDS: prospects of HIV-1 associated neurological complications

“…The genetic compartmentalization of viral variants in the CNS suggest that adaptive changes occur in response to unique constraints within the brain microenvironment, including specific target cell populations and immune selection pressures [54].…”