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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

The foamy viruses (FV) or spumaviruses are an ancient subfamily of retroviruses that infect a variety of vertebrates. FVs are endemic, but apparently apathogenic, in modern non-human primates. Like other retroviruses, FV replication is inhibited by type-I interferon (IFN). In a previously described screen of IFN-stimulated genes (ISGs), we identified the macaque PHD finger domain protein-11 (PHF11) as an inhibitor of prototype foamy virus (PFV) replication. Here, we show that human and macaque PHF11 inhibit the replication of multiple spumaviruses, but are inactive against several orthoretroviruses. Analysis of other mammalian PHF11 proteins revealed that antiviral activity is host species dependent. Using multiple reporter viruses and cell lines, we determined that PHF11 specifically inhibits a step in the replication cycle that is unique to FVs, namely basal transcription from the FV internal promoter (IP). In so doing, PHF11 prevents expression of the viral transactivator Tas and subsequent activation of the viral LTR promoter. These studies reveal a previously unreported inhibitory mechanism in mammalian cells, that targets a family of ancient viruses and may promote viral latency. Author summary: Foamy viruses have a unique replication strategy and long evolutionary relationship with their vertebrate hosts that has resulted in wide-spread infection of modern species without any apparent pathogenic consequence. How foamy virus infections are controlled by their hosts is unknown. Here, we demonstrate that infection of a variety of foamy viruses is inhibited by the interferon-stimulated gene product, PHF11, in a species-dependent manner. We show that PHF11 prevents replication by a previously undescribed mechanism, namely by inhibiting gene expression from an internal viral promoter, a conserved and distinct feature of the foamy viruses. Inhibition of early viral gene expression by PHF11 may promote viral latency and the apathogenicity of foamy viruses. [ABSTRACT FROM AUTHOR]

An essential step in the development of effective antiviral humoral responses is cytokine-triggered class switch recombination resulting in the production of antibodies of a specific isotype. Most viral and parasitic infections in mice induce predominantly IgG2a-specific antibody responses that are stimulated by interferon gamma (IFN-γ). However, in some mice deficient in IFN-γ, class switching to IgG2a antibodies is relatively unaffected, indicating that another signal(s) can be generated upon viral or parasitic infections that trigger this response. Here, we found that a single recessive locus, provisionally called IFN-γ-independent IgG2a (Igii), confers the ability to produce IFN-γ-independent production of IgG2a antibodies upon retroviral infection. The Igii locus was mapped to chromosome 9 and was found to function in the radiation-resistant compartment. Thus, our data implicate nonhematopoietic cells in activation of antiviral antibody responses in the absence of IFN-γ. [ABSTRACT FROM AUTHOR]

Summary Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs. [ABSTRACT FROM AUTHOR]

Myxovirus resistance 2 (Mx2/MxB) has recently been uncovered as an effector of the anti-HIV-1 activity of type I interferons (IFNs) that inhibits HIV-1 at an early stage postinfection, after reverse transcription but prior to proviral integration into host DNA. The mechanistic details of Mx2 antiviral activity are not yet understood, but a few substitutions in the HIV-1 capsid have been shown to confer resistance to Mx2. Through a combination of in vitro evolution and unbiased mutagenesis, we further map the determinants of sensitivity to Mx2 and reveal that multiple capsid (CA) surfaces define sensitivity to Mx2. Intriguingly, we reveal an unanticipated sensitivity determinant within the C-terminal domain of capsid. We also report that Mx2s derived from multiple primate species share the capacity to potently inhibit HIV-1, whereas selected nonprimate orthologs have no such activity. Like TRIM5, another CA targeting antiretroviral protein, primate Mx2s exhibit species-dependent variation in antiviral specificity against at least one extant virus and multiple HIV-1 capsid mutants. Using a combination of chimeric Mx2 proteins and evolution-guided approaches, we reveal that a single residue close to theNterminus that has evolved under positive selection can determine antiviral specificity. Thus, the variable Nterminal region can define the spectrum of viruses inhibited by Mx2. [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. [ABSTRACT FROM AUTHOR]

Many survival pathways influence B cell lifespan, yet how survival is regulated throughout B cell development is not fully understood. Non-engaged BCRs are thought to induce tonic signals critical for B cell survival and development. Cytokines are also known to influence B cell survival at many stages of development. It has been reported that a fraction of immature bone marrow B cells bind BAFF, a known B cell survival factor. Using 3-83Igi knock-in mice we are investigating the relationship between BCR and cytokine receptor signaling in immature B cell survival. We hypothesize that tonic signaling through non-autoreactive BCRs leads to the expression of BAFF-R on immature B cells, and the combination of survival signals through these receptors permits their further development and entry into the periphery. While we observe a positive correlation between the level of non-autoreactive BCR and BAFF-R expression on the surface of immature B cells, we are yet to find evidence that BAFF-R plays a functional role in the survival of B cells at this stage. However our data support the hypothesis that a threshold level of tonic BCR signal is required for B cell development, and suggests that the intensity of tonic BCR signals may be important for both the differentiation and survival of developing B cells. [ABSTRACT FROM AUTHOR]

Viruses, including retroviruses, can be passed from mothers to their progeny during birth and breastfeeding. It is assumed that newborns may develop immune tolerance to milk-transmitted pathogens similarly to food antigens. I/LnJ mice are uniquely resistant to retroviruses acquired as newborns or as adults as they produce virus-neutralizing antibodies (Abs). A loss-of-function allele of H2-Ob (Ob), originally mapped within the virus infectivity controller 1 (vic1) locus, is responsible for production of antiretrovirus Abs in I/LnJ mice. Importantly, Ob-deficient and vic1 I/LnJ congenic mice on other genetic backgrounds produce antivirus Abs when infected as adults, but not as newborns. We report here that I/LnJ mice carry an additional genetic locus, virus infectivity controller 2 (vic2), that abrogates neonatal immune tolerance to retroviruses. Further genetic analysis mapped the vic2 locus to the telomeric end of chromosome 15. Identification of the vic2 gene and understanding of the related signaling pathways would make blocking of neonatal immune tolerance to retroviruses an achievable goal. [ABSTRACT FROM AUTHOR]

Summary Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype. Subsequent bioinformatics and functional analyses of the human H2-Ob homolog, HLA-DOB, revealed both loss- and gain-of-function alleles, which could affect the ability of their carriers to control infections with human hepatitis B (HBV) and C (HCV) viruses. Thus, understanding of the previously unappreciated role of H2-O (HLA-DO) in immunity to infections may suggest new approaches in achieving neutralizing immunity to viruses. [ABSTRACT FROM AUTHOR]

Context: General neck pain is a prevalent complaint made by patients to their physicians and is often of a suspected musculoskeletal origin. Osteopathic manipulative treatment (OMT) is a form of manual therapy utilized by osteopathic physicians and some allopathic physicians to treat a broad variety of musculoskeletal ailments, including neck pain. Bio-Electro-Magnetic Energy Regulation (BEMER) is an emerging therapeutic modality that deploys a biorhythmically defined stimulus through a pulsed electromagnetic field and has been shown to reduce musculoskeletal pain. Studies on these treatments have independently yielded promising results. Therefore, it is possible that the utility of OMT and BEMER can produce an additive improvement in the treatment of neck pain., Objectives: The objectives of this study are to investigate the individual and combined effects of OMT and BEMER therapy on neck pain in adults., Methods: Adults with nonspecific neck pain were recruited for the study. A total of 44 participants met the study inclusion criteria and were randomized into one of four study groups: OMT-only, BEMER-only, OMT+BEMER, or CONTROL (light touch and sham). Forty subjects completed the study, and data for 38 participants were included in our analyses. An OMT and BEMER protocol were specifically designed for this study under the guidance of a licensed osteopathic physician. Participants underwent intervention for a duration of 3 weeks. Data were obtained through baseline and postintervention assessments utilizing three surveys: Neck Disability Index (NDI), Visual Analog Scale (VAS), and Short Form 12-item Health Survey (SF-12, divided into Mental and Physical). One-way analysis of variance (ANOVA) analysis was performed retrospectively on pre- and postintervention absolute means between study groups. Significance was set at p<0.05., Results: One-way ANOVA analysis demonstrated a statistically significant difference in pre- vs. postintervention mean scores between BEMER and CONTROL (p<0.05), BEMER compared to OMT (p<0.005), and BEMER compared to BEMER+OMT (p<0.05), in the NDI. The OMT+BEMER group reported an average reduction in pain on the VAS of 21.3 (±29.3) points, or a 65.0 % reduction of pain. A similarly substantial decrease in pain was reported in the BEMER study group, which showed a 46.2 % reduction in pain from baseline. The OMT and CONTROL study groups only reported a 2.9 and 23.9 % decrease, respectively. The BEMER and OMT+BEMER study groups also demonstrated a reduction in subjective reporting on the NDI, by 53.8 and 26.3 %, respectively. The BEMER study group also achieved the most substantial improvement in mental and physical well-being as reported by the SF-12., Conclusions: Study arms that incorporated BEMER yielded improvements on the NDI, VAS, and SF-12, indicating benefits to BEMER regarding improved overall functionality in routine daily activities as well as a reduction in nonspecific neck pain. Perceived pain, as demonstrated on the VAS, was seemingly improved in an additive fashion from the BEMER group to the OMT+BEMER group, although the results did not achieve statistical significance. Further study with greater participation could provide additional insight., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

HIV-1 inhibits the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) to prevent the induction of a proinflammatory state but also activates the NF-κB pathway to promote viral transcription. Thus, optimal regulation of this pathway is important for the viral life cycle. In recent work, Pickering et al . (3) demonstrate that HIV-1 viral protein U has contrasting effects on the two distinct paralogs of β-transducin repeat-containing protein (β-TrCP1 and β-TrCP2) and that this interaction has important implications for the regulation of both the canonical and non-canonical NF-κB pathways. Additionally, the authors identified the viral requirements for the dysregulation of β-TrCP. In this commentary, we discuss how these findings further our understanding of how the NF-κB pathway functions during viral infection., Competing Interests: The authors declare no conflict of interest

Inbred mouse lines vary in their ability to mount protective antiretroviral immune responses, and even closely related strains can exhibit opposing phenotypes upon retroviral infection. Here, we found that 129S mice inherit a previously unknown mechanism for the production of anti-murine leukemia virus (MLV) antibodies and control of infection. The resistant phenotype in 129S1 mice is controlled by two dominant loci that are independent from known MLV resistance genes. We also show that production of anti-MLV antibodies in 129S7 mice, but not 129S1 mice, is independent of interferon gamma signaling. Thus, our data indicate that 129S mice inherit an unknown mechanism for control of MLV infection and demonstrate that there is genetic variability in 129S substrains that affects their ability to mount antiviral immune responses. IMPORTANCE Understanding the genetic basis for production of protective antiviral immune responses is crucial for the development of novel vaccines and adjuvants. Additionally, characterizing the genetic and phenotypic variability in inbred mice has implications for the selection of strains for targeted mutagenesis, choice of controls, and for broader understanding of the requirements for protective immunity., Competing Interests: The authors declare no conflict of interest.

HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between the capsid protein (CA) and nucleoporins (Nups). Here, we show that HIV-1 CA can bind multiple Nups, and that both natural and manipulated variation in Nup levels impacts HIV-1 infection in a manner that is strikingly dependent on cell-type, cell-cycle, and cyclophilin A (CypA). We also show that Nups mediate the function of the antiviral protein MX2, and that MX2 can variably inhibit non-viral NLS function. Remarkably, both enhancing and inhibiting effects of cyclophilin A and MX2 on various HIV-1 CA mutants could be induced or abolished by manipulating levels of the Nup93 subcomplex, the Nup62 subcomplex, NUP88, NUP214, RANBP2, or NUP153. Our findings suggest that several Nup-dependent 'pathways' are variably exploited by HIV-1 to target host DNA in a cell-type, cell-cycle, CypA and CA-sequence dependent manner, and are differentially inhibited by MX2., Competing Interests: MK, SR, MT, TZ, MY, MK, PB No competing interests declared, (© 2018, Kane et al.)

The mouse mammary tumor virus (MMTV) Gag protein directs the assembly in the cytoplasm of immature viral capsids, which subsequently bud from the plasma membranes of infected cells. MMTV Gag localizes to discrete cytoplasmic foci in mouse mammary epithelial cells, consistent with the formation of cytosolic capsids. Unexpectedly, we also observed an accumulation of Gag in the nucleoli of infected cells derived from mammary gland tumors. To detect Gag-interacting proteins that might influence its subcellular localization, a yeast two-hybrid screen was performed. Ribosomal protein L9 (RPL9 or L9), an essential component of the large ribosomal subunit and a putative tumor suppressor, was identified as a Gag binding partner. Overexpression of L9 in cells expressing the MMTV(C3H) provirus resulted in specific, robust accumulation of Gag in nucleoli. Förster resonance energy transfer (FRET) and coimmunoprecipitation analyses demonstrated that Gag and L9 interact within the nucleolus, and the CA domain was the major site of interaction. In addition, the isolated NC domain of Gag localized to the nucleolus, suggesting that it contains a nucleolar localization signal (NoLS). To determine whether L9 plays a role in virus assembly, small interfering RNA (siRNA)-mediated knockdown was performed. Although Gag expression was not reduced with L9 knockdown, virus production was significantly impaired. Thus, our data support the hypothesis that efficient MMTV particle assembly is dependent upon the interaction of Gag and L9 in the nucleoli of infected cells.

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.

Most viral infections are self-limiting, resulting in either clearance of the pathogen or death of the host. However, a subset of viruses can establish permanent infection and persist indefinitely within the host. Even though persisting viruses are derived from various viral families with distinct replication strategies, they all utilize common mechanisms for establishment of long-lasting infections. Here, we discuss the commonalities between persistent infections with herpes-, retro-, flavi-, arena-, and polyomaviruses that distinguish them from acutely infecting viral pathogens. These shared strategies include selection of cell subsets ideal for long-term maintenance of the viral genome, modulation of viral gene expression, viral subversion of apoptotic pathways, and avoidance of clearance by the immune system.

B cells expressing two different Ig kappa L chains (allotype included) have been occasionally observed. To determine frequency and function of these cells, we have analyzed gene-targeted mice that carry a human and a mouse Igk C region genes. Using different methodologies, we found that cells expressing two distinct kappa-chains were 1.4-3% of all B cells and that they were present in the follicular, marginal zone, and B1 mature B cell subsets. When stimulated in vitro with anti-IgM, dual kappa surface-positive cells underwent activation that manifested with cell proliferation and/or up-regulation of activation markers and similar to single kappa-expressing B cells. Yet, when activated by divalent reagents that bound only one of the two kappa-chains, dual kappa B cells responded suboptimally in vitro, most likely because of reduced Ag receptor cross-linking. Nonetheless, dual kappa B cells participated in a SRBC-specific immune response in vivo. Finally, we found that Ig allotype-included B cells that coexpress autoreactive and nonautoreactive Ag receptors were also capable of in vitro responses following BCR aggregation. In summary, our studies demonstrate that Ig kappa allotype-included B cells are present in the mouse mature B cell population and are responsive to BCR stimulation both in vitro and in vivo. Moreover, because in vitro activation in response to anti-IgM was also observed in cells coexpressing autoreactive and nonautoreactive Abs, our studies suggest a potential role of allotype-included B cells in both physiological and pathological immune responses.

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.