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Avian leukosis virus (ALV), the prototypical alpharetrovirus, causes tumorigenesis, immunosuppression, and wasting disease in poultry. The ALV genus is classified into ten subgroups, which differ in their host range, cell tropism, and receptor usage. The subgroups A, B, K, and J cause significant economic losses worldwide. The most recently discovered subgroup, ALV-K, which is now widespread in China, has been shown to use the tva cell receptor and share it with ALV-A. However, the specific amino acid residues crucial for ALV-K host cell entry remain unknown. Using precise tva expression and chimeric tva receptors, we further elucidated the significance of the cysteine-rich domain in mediating interactions with both ALV-A and ALV-K. Through a comprehensive analysis of mutated tva receptor variants, we pinpointed tryptophan at position 33 (W33) as a pivotal amino acid residue essential for ALV-K virus binding and entry. Of note is the finding that the substitution of W33 induced resistance to ALV-K while preserving sensitivity to ALV-A. This study not only represents an advance in the understanding of the specificity of the tva receptor for ALV-K, but also offers a biotechnological strategy for the prevention of ALV-K infections in poultry.

The extent of virus transmission among individuals and species is generally determined by the presence of specific membrane-embedded virus receptors required for virus entry. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor is the first and crucial step in determining host specificity. Using a well-established retroviral model—avian Rous sarcoma virus (RSV)—we analyzed changes in an RSV variant that had repeatedly been able to infect rodents. By envelope gene (env) sequencing, we identified eight mutations that do not match the already described mutations influencing the host range. Two of these mutations—one at the beginning (D32G) of the surface Env subunit (SU) and the other at the end of the fusion peptide region (L378S)—were found to be of critical importance, ensuring transmission to rodent, human, and chicken cells lacking the appropriate receptor. Furthermore, we carried out assays to examine the virus entry mechanism and concluded that these two mutations cause conformational changes in the Env variant and that these changes lead to an activated, or primed, state of Env (normally induced after Env interaction with the receptor). In summary, our results indicate that retroviral host range extension is caused by spontaneous Env activation, which circumvents the need for original cell receptor. This activation is, in turn, caused by mutations in various env regions.

Interferon-induced transmembrane proteins (IFITMs) inhibit the entry of diverse enveloped viruses. The spectrum of antiviral activity of IFITMs is largely determined by their subcellular localization. IFITM1 localizes to and primarily blocks viral fusion at the plasma membrane, while IFITM3 prevents viral fusion in late endosomes by accumulating in these compartments. We and others have previously shown that cyclosporine treatment relieves the fusion block for the Influenza A virus, but the mechanism of this rescue remained unclear. Here, we report the existence of at least two distinct pools of IFITMs in cyclosporine treated cells. Major pools of IFITM1 and IFITM3 were found in endosomes, with IFITM1 relocating from the plasma membrane by a mechanism involving macropinocytosis, while the newly synthesized IFITMs were trapped in the Golgi. We noted that cyclosporine-mediated IFITM redistribution to late endosomes was not associated with its degradation. Importantly, cyclosporine treatment restricted antibody access to the cytoplasmic N-terminus but not to the extracellular C-terminus of IFITMs, consistent with IFITM sequestration in intraluminal vesicles of late endosomes. Indeed, super-resolution microscopy revealed that cyclosporine induces IFITM3 redistribution from the periphery to the interior of late endosomes. Together, our results imply that IFITMs relocate to intraluminal vesicles of late endosomes in the presence of cyclosporine, thereby enabling viral fusion with the limiting membrane of these compartments. Our findings highlight the critical role of IFITM trafficking in antiviral defense and suggest a novel mechanism through which cyclosporine modulates the cell's susceptibility to viral infections.

Interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral factors that restrict the entry of many enveloped viruses, including HIV-1, by modifying host membrane properties and trapping fusion at the hemifusion stage. Beyond blocking entry in target cells, IFITMs also reduce the infectivity of virions produced from IFITM-expressing cells, a phenomenon termed “negative imprinting”. Conserved motifs, such as the amphipathic helix and oligomerization motifs, have been reported to be essential for IFITM-mediated protection of target cells from viral infection. Yet, the impact of IFITM incorporation on progeny virion infectivity remains poorly defined. Here, we show that IFITM3 mutants defective in target cell protection activity still markedly impair HIV-1 fusion/infection upon incorporating into virions, without affecting viral maturation or Env incorporation. Immunofluorescence studies suggest mislocalization of the IFITM3 mutants as the reason for the lack of antiviral activity in target cells. Testing the antiviral activity of chimeras between antiviral and non-antiviral IFITM orthologs failed to clearly identify a domain responsible for reduction of HIV-1 infectivity, suggesting that multiple domains may be required for negative imprinting. Interestingly, co-incorporation of non-antiviral dog IFITM1 with human IFITM3 did not interfere with IFITM3’s negative imprinting activity, despite forming mixed hetero-oligomers. This finding implies a dominant, oligomerization-independent antiviral phenotype of IFITM3 in virions. Our findings suggest that IFITMs may protect target cells and negatively imprint progeny virions through distinct mechanisms, underscoring the need to further characterize the molecular basis for the reduced fusion competence of IFITM-containing HIV-1 particles.

Interferon-induced transmembrane proteins (IFITMs) block the fusion of diverse enveloped viruses, likely through increasing the cell membrane’s rigidity. Previous studies have reported that the antiviral activity of the IFITM family member, IFITM3, is antagonized by cell pretreatment with rapamycin derivatives and cyclosporines A and H (CsA and CsH) that promote the degradation of IFITM3. Here, we show that CsA and CsH potently enhance virus fusion with IFITM1- and IFITM3-expressing cells by inducing their rapid relocalization from the plasma membrane and endosomes, respectively, towards the Golgi. This relocalization is not associated with a significant degradation of IFITMs. Although prolonged exposure to CsA induces IFITM3 degradation in cells expressing low endogenous levels of this protein, its levels remain largely unchanged in interferon-treated cells or cells ectopically expressing IFITM3. Importantly, the CsA-mediated redistribution of IFITMs to the Golgi occurs on a much shorter time scale than degradation and thus likely represents the primary mechanism of enhancement of virus entry. We further show that rapamycin also induces IFITM relocalization toward the Golgi, albeit less efficiently than cyclosporines. Our findings highlight the importance of regulation of IFITM trafficking for its antiviral activity and reveal a novel mechanism of the cyclosporine-mediated modulation of cell susceptibility to enveloped virus infection.

Interferon-induced transmembrane proteins (IFITMs) block the fusion of diverse enveloped viruses, likely through increasing the cell membrane's rigidity. Previous studies have reported that the antiviral activity of the IFITM family member, IFITM3, is antagonized by cell pretreatment with rapamycin derivatives and cyclosporines A and H (CsA and CsH) that promote the degradation of IFITM3. Here, we show that CsA and CsH potently enhance virus fusion with IFITM1- and IFITM3-expressing cells by inducing their rapid relocalization from the plasma membrane and endosomes, respectively, towards the Golgi. This relocalization is not associated with a significant degradation of IFITMs. Although prolonged exposure to CsA induces IFITM3 degradation in cells expressing low endogenous levels of this protein, its levels remain largely unchanged in interferon-treated cells or cells ectopically expressing IFITM3. Importantly, the CsA-mediated redistribution of IFITMs to the Golgi occurs on a much shorter time scale than degradation and thus likely represents the primary mechanism of enhancement of virus entry. We further show that rapamycin also induces IFITM relocalization toward the Golgi, albeit less efficiently than cyclosporines. Our findings highlight the importance of regulation of IFITM trafficking for its antiviral activity and reveal a novel mechanism of the cyclosporine-mediated modulation of cell susceptibility to enveloped virus infection.

Interferon-induced transmembrane proteins (IFITMs) inhibit the entry of diverse enveloped viruses. The spectrum of antiviral activity of IFITMs is largely determined by their subcellular localization. IFITM1 localizes to and primarily blocks viral fusion at the plasma membrane, while IFITM3 prevents viral fusion in late endosomes by accumulating in these compartments. We have previously reported that cyclosporine A (CsA) treatment relieves the fusion block for the Influenza A virus, likely by relocating IFITM1 and IFITM3 from the plasma membrane and endosomes, respectively, to the Golgi area. Here, we report the existence of at least two distinct pools of IFITMs in CsA treated cells. While immunostaining of CsA treated cells using mild permeabilization agents, such as digitonin, suggests preferential IFITM localization at the Golgi apparatus, a harsher permeabilization protocol reveals a large, previously unidentified pool of IFITMs in late endosomes. Notably, IFITM redistribution was not associated with its degradation. A disproportionate loss of antibody access to the cytoplasmic N-terminus compared to the extracellular C-terminus of IFITMs after CsA treatment is consistent with sequestration of the N-terminal domain inside intraluminal vesicles of late endosomes. Accordingly, super-resolution microscopy reveals that CsA induces IFITM3 redistribution from the periphery to the interior of late endosomes. Together, our results imply that IFITMs relocate to intraluminal vesicles of late endosomes in the presence of CsA, thereby enabling viral fusion with the limiting membrane of these compartments. Our findings highlight the critical role of IFITM trafficking in antiviral defense and suggest a novel mechanism through which CsA modulates the cell's susceptibility to viral infections.

The paper proposes a new soil evaluation system using the principle of the Saaty method. The Saaty method has been modified and named Soil Assessment System (SAS). Significance weights are assigned to individual soil characteristics (indicators). This provides a more detailed differentiation of the significance of the indicator on soil quality and a more accurate assessment, especially in marginal cases where the assessment by the methods used so far has not been fully conclusive. In addition to physico-chemical properties, other criteria are taken into account to assess not only productional but also non-productional functions. The possibility of using indicators referring to a broader context (e.g., soil sealing value) is also important, thus enabling a comprehensive assessment of the quality of the land. This results in points for individual sampling locations. Soils are categorized according to the number of points and results are shown on maps.

Archaeoichthyological research is not well developed in Czech archaeology, partly because of the country’s landlocked position. Nonetheless, fishing, fish consumption, and the fish trade played important roles in the Czech lands in the Middle and Early Modern Ages. This paper presents, as a case study, detailed documentation and analysis of a few archaeological bone finds from Prague determined as imported marine fish, and introduces this specialised field of research more generally. Beyond the archaeological bone finds, we conduct an in-depth analysis of historical written records of the marine fish trade in the Czech lands. A basic review of current archaeozoological knowledge of marine fish finds, especially cod and herring, which played the most important role in the long-distance fish trade is also provided. An important contribution — the first of its kind in Czech archaeology — is the use of carbon, nitrogen, and sulphur stable isotope analysis to determine the provenance of cod found at Prague Castle.

During minor to moderate geomagnetic storms, caused by corotating interaction regions (CIRs) at the leading edge of high-speed streams (HSSs), solar wind Alfvén waves modulated the magnetic reconnection at the dayside magnetopause. The Resolute Bay Incoherent Scatter Radars (RISR-C and RISR-N), measuring plasma parameters in the cusp and polar cap, observed ionospheric signatures of flux transfer events (FTEs) that resulted in the formation of polar cap patches. The patches were observed as they moved over the RISR, and the Canadian High-Arctic Ionospheric Network (CHAIN) ionosondes and GPS receivers. The coupling process modulated the ionospheric convection and the intensity of ionospheric currents, including the auroral electrojets. The horizontal equivalent ionospheric currents (EICs) are estimated from ground-based magnetometer data using an inversion technique. Pulses of ionospheric currents that are a source of Joule heating in the lower thermosphere launched atmospheric gravity waves, causing traveling ionospheric disturbances (TIDs) that propagated equatorward. The TIDs were observed in the SuperDual Auroral Radar Network (SuperDARN) high-frequency (HF) radar ground scatter and the detrended total electron content (TEC) measured by globally distributed Global Navigation Satellite System (GNSS) receivers.