The Antiviral Activity of the Cellular Glycoprotein LGALS3BP/90K Is Species Specific.

Cellular antiviral proteins interfere with distinct steps of replication cycles of viruses. The galectin 3 binding protein (LGALS3BP, also known as 90K) was previously shown to lower the infectivity of nascent human immunodeficiency virus type 1 (HIV-1) virions when expressed in virus-producing cells. This antiviral effect was accompanied by impaired gp160Env processing and reduced viral incorporation of mature Env glycoproteins. Here, we examined the ability of 90K orthologs from primate species to reduce the particle infectivity of distinct lentiviruses. We show that 90K's ability to diminish the infectivity of lentiviral particles is conserved within primate species, with the notable exception of 90K from rhesus macaque. Comparison of active and inactive 90K orthologs and variants uncovered the fact that inhibition of processing of the HIV-1 Env precursor and reduction of cell surface expression of HIV-1 Env gp120 are required, but not sufficient, for 90K-mediated antiviral activity. Rather, 90K-mediated reduction of virion-associated gp120 coincided with antiviral activity, suggesting that 90K impairs the incorporation of HIV-1 Env into budding virions. We show that a single "humanizing" amino acid exchange in the BTB (broad-complex, tramtrack, and bric-à-brac)/POZ (poxvirus and zinc finger) domain is sufficient to fully rescue the antiviral activity of a shortened version of rhesus macaque 90K, but not that of the full-length protein. Comparison of the X-ray structures of the BTB/POZ domains of 90K from rhesus macaques and humans point toward a slightly larger hydrophobic patch at the surface of the rhesus macaque BTB domain that may modulate a direct interaction with either a second 90K domain or a different protein. <b>IMPORTANCE</b> The cellular 90K protein has been shown to diminish the infectivity of nascent HIV-1 particles. When produced in 90K-expressing cells, particles bear smaller amounts of the HIV-1 Env glycoprotein, which is essential for attaching to and entering new target cells in the subsequent infection round. However, whether the antiviral function of 90K is conserved across primates is unknown. Here, we found that 90K orthologs from most primate species, but, surprisingly, not from rhesus macaques, inhibit HIV-1. The introduction of a single amino acid exchange into a short version of the rhesus macaque 90K protein, consisting of the two intermediate domains of 90K, resulted in full restoration of antiviral activity. Structural elucidation of the respective domain suggests that the absence of antiviral activity in the rhesus macaque factor may be linked to a subtle change in protein-protein interaction

The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals

Background: The presence of a vpx gene distinguishes HIV-2 from HIV-1, the main causative agent of AIDS. Vpx degrades the restriction factor SAMHD1 to boost HIV-2 infection of macrophages and dendritic cells and it has been suggested that the activation of antiviral innate immune responses after Vpx-dependent infection of myeloid cells may explain why most HIV-2-infected individuals efficiently control viral replication and become long-term survivors. However, the role of Vpx-mediated SAMHD1 antagonism in the virological and clinical outcome of HIV-2 infection remained to be investigated. Results: Here, we analyzed the anti-SAMHD1 activity of vpx alleles derived from seven viremic and four long-term aviremic HIV-2-infected individuals. We found that effective Vpx-mediated SAMHD1 degradation and enhancement of myeloid cell infection was preserved in most HIV-2-infected individuals including all seven that failed to control the virus and developed AIDS. The only exception were vpx alleles from an aviremic individual that predicted a M68K change in a highly conserved nuclear localization signal which disrupted the ability of Vpx to counteract SAMHD1. We also found that HIV-2 is less effective than HIV-1 in inducing innate immune activation in dendritic cells. Conclusions: Effective immune control of viral replication in HIV-2-infected individuals is not associated with increased Vpx-mediated degradation of SAMHD1

From upright to upside-down presentation: A spatio-temporal ERP study of the parametric effect of rotation on face and house processing

<p>Abstract</p> <p>Background</p> <p>While there is a general agreement that picture-plane inversion is more detrimental to face processing than to other seemingly complex visual objects, the origin of this effect is still largely debatable. Here, we address the question of whether face inversion reflects a quantitative or a qualitative change in processing mode by investigating the pattern of event-related potential (ERP) response changes with picture plane rotation of face and house pictures. Thorough analyses of topographical (Scalp Current Density maps, SCD) and dipole source modeling were also conducted.</p> <p>Results</p> <p>We find that whilst stimulus orientation affected in a similar fashion participants' response latencies to make face and house decisions, only the ERPs in the N170 latency range were modulated by picture plane rotation of faces. The pattern of N170 amplitude and latency enhancement to misrotated faces displayed a curvilinear shape with an almost linear increase for rotations from 0° to 90° and a dip at 112.5° up to 180° rotations. A similar discontinuity function was also described for SCD occipito-temporal and temporal current foci with no topographic distribution changes, suggesting that upright and misrotated faces activated similar brain sources. This was confirmed by dipole source analyses showing the involvement of bilateral sources in the fusiform and middle occipital gyri, the activity of which was differentially affected by face rotation.</p> <p>Conclusion</p> <p>Our N170 findings provide support for both the quantitative and qualitative accounts for face rotation effects. Although the qualitative explanation predicted the curvilinear shape of N170 modulations by face misrotations, topographical and source modeling findings suggest that the same brain regions, and thus the same mechanisms, are probably at work when processing upright and rotated faces. Taken collectively, our results indicate that the same processing mechanisms may be involved across the whole range of face orientations, but would operate in a non-linear fashion. Finally, the response tuning of the N170 to rotated faces extends previous reports and further demonstrates that face inversion affects perceptual analyses of faces, which is reflected within the time range of the N170 component.</p

Filling-in of the foveal blue scotoma.

The blue-blindness (tritanopia) of the human foveola normally goes unnoticed but can be directly visualized by having observers view a flickering, monochromatic, short-wavelength field. The blue scotoma appears as a tiny dark spot in central vision, the visibility of which depends upon the wavelength of the field and the temporal frequency of modulation. Comparisons of fading times as a function of flicker frequency for the blue scotoma, foveal afterimages and optically stabilized images indicate a common time course, consistent with the hypothesis that perceptual filling-in of the foveal blue scotoma reflects the operation of neural processes similar to those involved in fading and regeneration of stabilized images

Filling-in of the foveal blue scotoma.

The blue-blindness (tritanopia) of the human foveola normally goes unnoticed but can be directly visualized by having observers view a flickering, monochromatic, short-wavelength field. The blue scotoma appears as a tiny dark spot in central vision, the visibility of which depends upon the wavelength of the field and the temporal frequency of modulation. Comparisons of fading times as a function of flicker frequency for the blue scotoma, foveal afterimages and optically stabilized images indicate a common time course, consistent with the hypothesis that perceptual filling-in of the foveal blue scotoma reflects the operation of neural processes similar to those involved in fading and regeneration of stabilized images