To establish chronic infections, viruses must develop strategies to evade the host's immune responses. Many retroviruses, including mouse mammary tumor virus (MMTV), are transmitted most efficiently through mucosal surfaces rich in microbiota. We found that MMTV, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. This process required intestinal microbiota, as antibiotic-treated mice or germ-free did not transmit infectious their offspring....

Highlights•ISG screening identifies direct and indirect antiretroviral proteins•Interferon-γ inhibits HIV-1 through IDO1-mediated tryptophan depletion•TRIM56 enhances the potential of interferon-αSummaryInterferons (IFNs) exert their anti-viral effects by inducing expression hundreds IFN-stimulated genes (ISGs). The activity known ISGs is insufficient to account for IFN, suggesting that with are yet be described. We constructed an arrayed library from rhesus macaques tested ability...

ABSTRACT Interlinked interactions between the viral capsid (CA), nucleoporins (Nups), and antiviral protein myxovirus resistance 2 (MX2/MXB) influence human immunodeficiency virus 1 (HIV-1) nuclear entry outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in HIV-1 import MX2 activity, mechanism by which RANBP2 facilitates infection is not well understood. To explore MX2, CA, RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing from...

ABSTRACT Myxovirus resistance 2 (Mx2/MxB) has recently been uncovered as an effector of the anti-HIV-1 activity type I interferons (IFNs) that inhibits HIV-1 at early stage postinfection, after reverse transcription but prior to proviral integration into host DNA. The mechanistic details Mx2 antiviral are not yet understood, a few substitutions in capsid have shown confer Mx2. Through combination vitro evolution and unbiased mutagenesis, we further map determinants sensitivity reveal...

HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between capsid protein (CA) and nucleoporins (Nups). Here, we show that CA can bind multiple Nups, both natural manipulated variation in Nup levels impacts infection manner is strikingly dependent on cell-type, cell-cycle, cyclophilin A (CypA). We also Nups mediate function antiviral MX2, MX2 variably inhibit non-viral NLS function. Remarkably, enhancing inhibiting effects...

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) major determinant for sensitivity to MX2, and complex interactions between CA, nucleoporins (Nups), cyclophilin A (CypA), other cellular proteins influence outcome infection. To explore CypA, we utilized a CRISPR-Cas9/AAV approach generate CypA knock-out cell lines as well...

Abstract Human immunodeficiency virus type 1 (HIV-1) capsid, which is the target of antiviral lenacapavir, protects viral genome and binds multiple host proteins to influence intracellular trafficking, nuclear import, integration. Previously, we showed that capsid binding cleavage polyadenylation specificity factor 6 (CPSF6) in cytoplasm competitively inhibited by cyclophilin A (CypA) regulates infection. Here determined a mutant with increased CypA affinity had significantly reduced entry...

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) capsid, which is the target of antiviral lenacapavir, protects viral genome and binds multiple host proteins to influence intracellular trafficking, nuclear import, integration. Previously, we showed that capsid binding cleavage polyadenylation specificity factor 6 (CPSF6) in cytoplasm competitively inhibited by cyclophilin A (CypA) regulates infection. Here, determined a mutant with increased CypA affinity had significantly reduced entry...

The S1 genome segment of avian reovirus strain S1133 was cloned and completely sequenced. sequence comprised 1636 bp with three distinct open reading frames (ORFs), suggesting the gene polycistronic in nature. ORFs from 5′ to 3′ were predicted encode polypeptides 9.8, 3.8 34.9 kDa, respectively. Of ORFs, only third possessed AUG initiation codon an optimum context for translation. ORF-encoded protein, 326 amino acids length, expressed Escherichia coli used as antigen immunoblots. protein...

Abstract Polyclonal goat anti-idiotypic Abs directed against anti-human gastrointestinal carcinoma mAb GA733 were administered to 13 colon cancer patients who had their primary tumor and lymph node metastases removed before immunotherapy. Patients received four s.c. doses (0.5 8 mg each) of alum-precipitated Ab. Seven the produced anti-anti-Ids that bound specifically epitope on cells shared idiotopes with GA733. In seven responding patients, anti-Id therapy modulated T cell responses. two...

The mouse mammary tumor virus (MMTV) Gag protein directs the assembly in cytoplasm of immature viral capsids, which subsequently bud from plasma membranes infected cells. MMTV localizes to discrete cytoplasmic foci epithelial cells, consistent with formation cytosolic capsids. Unexpectedly, we also observed an accumulation nucleoli cells derived gland tumors. To detect Gag-interacting proteins that might influence its subcellular localization, a yeast two-hybrid screen was performed....

Abstract B cells expressing two different Igκ L chains (allotype included) have been occasionally observed. To determine frequency and function of these cells, we analyzed gene-targeted mice that carry a human mouse Igk C region genes. Using methodologies, found distinct κ-chains were 1.4–3% all they present in the follicular, marginal zone, B1 mature cell subsets. When stimulated vitro with anti-IgM, dual κ surface-positive underwent activation manifested proliferation and/or up-regulation...

To replicate in a new host, lentiviruses must adapt to exploit required host factors and evade species-specific antiviral proteins. Understanding how protein variation drives lentivirus adaptation allowed us expand the range of HIV-1 pigtail macaques. We have previously derived viral swarm (in blood infected animals) that can cause AIDS this host. further reagent, we generated infectious molecular clones (IMCs) from swarm. identified with high replicative capacity peripheral mononuclear...

The foamy viruses (FV) or spumaviruses are an ancient subfamily of retroviruses that infect a variety vertebrates. FVs endemic, but apparently apathogenic, in modern non-human primates. Like other retroviruses, FV replication is inhibited by type-I interferon (IFN). In previously described screen IFN-stimulated genes (ISGs), we identified the macaque PHD finger domain protein-11 (PHF11) as inhibitor prototype virus (PFV) replication. Here, show human and PHF11 inhibit multiple spumaviruses,...

ABSTRACT Antiviral adaptive immune defenses consist of humoral and cell-mediated responses, which together eliminate extracellular intracellular virus. As most retrovirus-infected individuals do not raise efficient protective antivirus the relative importance responses in restraining retroviral infection is well understood. We utilized retrovirus-resistant I/LnJ mice, control with mouse mammary tumor virus (MMTV) murine leukemia (MuLV) via an mechanism, to assess contribution cellular...

Abstract 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) major determinant for sensitivity to MX2, and complex interactions between CA, nucleoporins (Nups), cyclophilin A (CypA), other cellular proteins influence outcome infection. To explore CypA, we utilized a CRISPR-Cas9/AAV approach generate CypA knock-out cell lines...

Understanding the signals that stimulate antibody production and class switch recombination to specific isotypes is crucial for development of novel vaccines adjuvants. While an interferon gamma-mediated IgG2a isotype upon viral infection in mice has been well established, this investigation reveals a noncanonical, gamma-independent pathway antiretroviral controlled by single recessive locus. Furthermore, study indicates radiation-resistant compartment can direct antiviral responses,...

Abstract Interlinked interactions between the viral capsid (CA), nucleoporins (Nups), antiviral protein myxovirus resistance 2 (MX2/MXB) influence HIV-1 nuclear entry and outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in import MX2 activity, mechanism by which RANBP2 facilitates infection is not well understood. To explore MX2, CA, RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing from its endogenous locus but lacking...