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Human myxovirus resistance 2 (MX2/MXB) is an interferon-induced GTPase that inhibits human immunodeficiency virus-1 (HIV-1) infection by preventing nuclear import of the viral preintegration complex. The HIV-1 capsid (CA) is the major viral determinant for sensitivity to MX2, and complex interactions between MX2, CA, nucleoporins (Nups), cyclophilin A (CypA), and other cellular proteins influence the outcome of viral infection. To explore the interactions between MX2, the viral CA, and CypA, we utilized a CRISPR-Cas9/AAV approach to generate CypA knock-out cell lines as well as cells that express CypA from its endogenous locus, but with specific point mutations that would abrogate CA binding but should not affect enzymatic activity or cellular function. We found that infection of CypA knock-out and point mutant cell lines with wild-type HIV-1 and CA mutants recapitulated the phenotypes observed upon cyclosporine A (CsA) addition, indicating that effects of CsA treatment are the direct result of blocking CA-CypA interactions and are therefore independent from potential interactions between CypA and MX2 or other cellular proteins. Notably, abrogation of GTP hydrolysis by MX2 conferred enhanced antiviral activity when CA-CypA interactions were abolished, and this effect was not mediated by the CA-binding residues in the GTPase domain, or by phosphorylation of MX2 at position T151. We additionally found that elimination of GTPase activity also altered the Nup requirements for MX2 activity. Our data demonstrate that the antiviral activity of MX2 is affected by CypA-CA interactions in a virus-specific and GTPase activity-dependent manner. These findings further highlight the importance of the GTPase domain of MX2 in regulation of substrate specificity and interaction with nucleocytoplasmic trafficking pathways. Author summary: HIV-1 entry into the nucleus is an essential step in viral replication that involves complex interactions between the viral capsid and multiple cellular proteins, including the proline isomerase cyclophilin A. Nuclear entry of HIV-1 and other primate lentiviruses is inhibited by the antiviral protein MX2. Here, we show that direct interactions between capsid and cyclophilin A affect the antiviral activity and specificity of MX2, and that these interactions are altered when the enzymatic activity of MX2 is eliminated. We demonstrate that abolishing enzymatic activity of MX2 also alters the requirements for nuclear pore complex components for viral restriction. Our study provides new insights into how the enzymatic function of MX2 affects inhibition of lentiviral nuclear import. [ABSTRACT FROM AUTHOR]

The bulk of solar flare energy is deposited in the chromosphere. Flare ribbons and footpoints in the chromosphere therefore offer great diagnostic potential of flare energy release and transport processes. High-quality observations from the Interface Region Imaging Spectrograph (IRIS) spacecraft have transformed our view of the Sun's atmospheric response to flares. Since most of the chromospheric lines observed by IRIS are optically thick, forward modelling is required to fully appreciate and extract the information they carry. Reproducing certain aspects of the Mg  ii lines remain frustratingly out of reach in state-of-the-art flare models, which are unable to satisfactorily reproduce the very broad-line profiles. A commonly proposed resolution to this is to assert that very large values of 'microturbulence' is present. We assess the validity of that approach by analysing optically thin lines in the flare chromosphere from the X-class flare SOL2014-10-25T17:08:00, using the derived value of non-thermal width as a constraint to our numerical models. A non-thermal width of the order 10 km s−1 was found within the short-lived red wing components of three spectral lines, with relatively narrow stationary components. Simulations of this flare were produced, and in the post-processing spectral synthesis we include within the downflows a microturbulence of 10 km s−1. While we can reproduce the O  i 1355.598 Å line rather well, and we can capture the general shape and properties of the Mg  ii line, the synthetic lines are still too narrow. [ABSTRACT FROM AUTHOR]

HIV-1 replication can be inhibited by type I interferon (IFN), and the expression of a number of gene products with anti-HIV-1 activity is induced by type I IFN (1,2). However, none of the known antiretroviral proteins can account for the ability of type I IFN to inhibit early, preintegration phases of the HIV-1 replication cycle in human cells (3,4). Here, by comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFN-α at early steps of the HIV-1 replication cycle, we identify myxovirus resistance 2 (MX2) as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA interference reduces the anti-HIV-1 potency of IFN-α. HIV-1 reverse transcription proceeds normally in MX2-expressing cells, but 2-long terminal repeat circular forms of HIV-1 DNA are less abundant, suggesting that MX2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that are known, or suspected, to alter the nuclear import pathways used by HIV-1 confer resistance to MX2, whereas preventing cell division increases MX2 potency. Overall, these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes., We and others have previously identified proteins with antiretroviral activity on the basis of their differential expression in cells that are permissive or non-permissive with respect to particular steps in [...]

There are no published data on the reliability of competitive strength performance, even though it has a pronounced effect on athletes' medal prospects and the ability of coaches and athletes to identify factors that affect competitive performance. The purpose of this investigation was to analyze the reliability of elite olympic weightlifters over a series of international weightlifting meets. We obtained official results of international competitions over an 18-month period from 1999 until the 2000 Olympic Games at the International Weightlifting Federation website. The measure of reliability was the typical within-athlete variation, derived as the coefficient of variation (CV) by 2-way analysis of variance of log-transformed weights lifted for the snatch, clean and jerk, and total. The results of this analysis were (a) within-athlete variations were as follows: snatch, 2.7% (95% likely range, 2.4-3.2%); clean and jerk, 2.3% (1.7-3.6%); total weight lifted, 2.5% (2.2-2.9%); (b) men and women: the variation was higher for the women compared with the men in both snatch (ratio of CV, 1.4) and clean and jerk (ratio of CV, 1.5), and for the total weight lifted (ratio of CV, 1.3); and (c) the top 5 athletes were almost always more reliable than the bottom-half athletes. Recent work has shown that the smallest worthwhile performance is about half the within-athlete variation, so coaches and sport scientists should focus on enhancements of as little as 1.2% in total weight lifted for elite olympic weightlifters. KEY WORDS. reliability, olympic weightlifting, coefficient of variation, elite athletes

Antiviral adaptive immune defenses consist of humoral and cell-mediated responses, which together eliminate extracellular and intracellular virus. As most retrovirus-infected individuals do not raise efficient protective antivirus immune responses, the relative importance of humoral and cell-mediated responses in restraining retroviral infection is not well understood. We utilized retrovirus-resistant I/LnJ mice, which control infection with mouse mammary tumor virus (MMTV) and murine leukemia virus (MuLV) via an adaptive immune mechanism, to assess the contribution of cellular responses and virus-neutralizing antibodies (Abs) to the control of retroviral infection. We found that in retrovirus-infected CD8-deficient I/LnJ mice, viral titers exceed the neutralizing capability of antiviral Abs, resulting in augmented virus spread and disease induction. Thus, even in the presence of robust neutralizing Ab responses, CD8-mediated responses are essential for full protection against retroviral infection. [ABSTRACT FROM AUTHOR]

Antiviral adaptive immune defenses consist of humoral and cell-mediated responses, which together eliminate extracellular and intracellular virus. As most retrovirus-infected individuals do not raise efficient protective antivirus immune responses, the relative importance of humoral and cell-mediated responses in restraining retroviral infection is not well understood. We utilized retrovirus-resistant I/LnJ mice, which control infection with mouse mammary tumor virus (MMTV) and murine leukemia virus (MuLV) via an adaptive immune mechanism, to assess the contribution of cellular responses and virus-neutralizing antibodies (Abs) to the control of retroviral infection. We found that in retrovirus-infected CD8-deficient I/LnJ mice, viral titers exceed the neutralizing capability of antiviral Abs, resulting in augmented virus spread and disease induction. Thus, even in the presence of robust neutralizing Ab responses, CD8-mediated responses are essential for full protection against retroviral infection.

The purpose of this study was to monitor the stress-induced alteration in concentrations of salivary immunoglobulin (S-IgA) and cortisol and the incidence of upper respiratory tract infections (URTI) over the course of a 9-week competitive season in college student-athletes and college students. The subjects consisted of 14 NCAA Division III collegiate female soccer athletes (19.8 ± 1.0 years, mean ± SD) and 14 female college students (22.5 ± 2.6 years). Salivary samples were collected for 9 weeks during a competitive soccer season. S-IgA and cortisol concentrations were determined by enzyme linked immunosorbent assay (ELISA). A training and performance questionnaire was given to the subjects every week, to record the subjects' session rating of perceived exertion (RPE) for all the training, load, monotony and strain, as well as any injuries or illnesses experienced. The between groups ANOVA procedure for repeated measures showed no changes in salivary concentrations of IgA and cortisol. Chi-square analysis showed that during the 9-week training season injury and illness occurred at a higher rate among the soccer players. There was a significant difference at baseline between soccer and control S-IgA levels (p≤0.05). Decreased levels of S-IgA and increases in the indices of training (load, strain and monotony) were associated with an increase in the incidence of illness during the 9-week competitive soccer season. Key PointsThere was a significant difference at baseline between soccer and control S-IgA levelsEighty-two percent of illnesses could be explained by a preceding decrease in S-IgA.Increases in the indices of training (load, strain and monotony) were associated with an increase in the incidence of illness.