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Human T-lymphotropic virus (HTLV) is a human, single-stranded RNA retrovirus that causes T-cell leukemia and T-cell lymphoma. The virus activates a subset of T-helper cellscalled Th1cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-gamma and TNF-alpha). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly Th2 dependant response (these include parasitic infections and production of mucosal and humoral antibodies).

Treponema pallidum is a gram-negative spirochaete bacterium and is considered to be metabolically crippled. There are at least four known subspecies: T. pallidum pallidum, T. pallidum pertenue, T. pallidum carateum and T. pallidum endemicum. The helical structure of T. pallidum pallidum allows it to move in a corkscrew motion through viscous mediums such as mucus. Treponema pallidum sub sp. pallidum has one of the smallest bacterial genomes at 1.14 million base pairs (Mb) and has limited metabolic capabilities, reflecting its adaptation through genome reduction to the rich environment of mammalian tissue.

Peptidase Inhibitor 16 (PI16) which a member of the CRISP family, is a putative serine protease inhibitor. PI16 interacts with PSP94/MSMB. PI16 is expressed in the prostate, testis, ovary and intestine. It also concentrates in prostate cancer patient's sera. PI16 may serve as a marker following prostatectomy for prostate cancer.

HIV-1 and HIV-2 appear to package their RNA differently. HIV-1 binds to any appropriate RNA whereas HIV-2 preferentially binds to mRNA which creates the Gag protein itself. This means that HIV-1 is better able to mutate. HIV-2 is transmitted in the same ways as HIV-1: Through exposure to bodily fluids such as blood, semen, tears and vaginal fluids. Immunodeficiency develops more slowly with HIV-2.
HIV-2 is less infectious in the early stages of the virus than with HIV-1.
The infectiousness of HIV-2 increases as the virus progresses.
Major differences include reduced pathogenicity of HIV-2 relative to HIV-1, enhanced immune control of HIV-2 infection and often some degree of CD4-independence. Despite considerable sequence and phenotypic differences between HIV-1 and 2 envelopes, structurally they are quite similar. Both membrane-anchored proteins eventually form the 6-helix bundles from the N-terminal and C-terminal regions of the ectodomain, which is common to many viral and cellular fusion proteins and which seems to drive fusion.
HIV-1 gp41 helical regions can form more stable 6-helix bundles than HIV-2 gp41 helical regions however HIV-2 fusion occurs at a lower threshold temperature (25°C), does not require Ca2+ in the medium, is insensitive to treatment of target cells with cytochalasin B, and is not affected by target membrane glycosphingolipid composition.

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now officially named CCL3 and CCL4 respectively. Both are major factors produced by macrophages after they are stimulated with bacterial endotoxins. They activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-a from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.

Insulin Receptor (INSR) is a receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. Once the precursor signal peptide is removed, the insulin receptor precursor is post-translationally cleaved into 2 chains (alpha and beta) which are covalently linked. Insulin binding initiates phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins function as docking proteins for other signaling proteins which contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2.

SARS Coronavirus is an enveloped virus containing three outer structural proteins, namely the membrane (M), envelope (E), and spike (S) proteins. Spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies.It has recently been shown that SARS is caused by a human coronavirus. Human coronaviruses are the major cause of upper respiratory tract illness in humans, such as the common cold. Coronaviruses are positive-stranded RNA viruses, featuring the largest viral RNA genomes known to date (27-31 kb). The first step in coronavirus infection is binding of the viral spike protein, a 139-kDa protein, to certain receptors on host cells. The spike protein is the main surface antigen of the coronavirus. The most prominent protein in the culture supernatants infected with SARS virus is a 46 kDa nucleocapsid protein. This suggests that the nucleocapsid protein is a major immunogen that may be useful for early diagnostics.

Anthrax PA (Protective Antigen) and Anthrax LF (Lethal Factor), along with Anthrax EF (Edema Factor), are toxins produced by Bacillus anthracis. All three of the proteins must be present for toxicity to occur. It begins with the binding of PA to its cell-surface receptor, ATR (Anthrax Toxin Receptor), at which point PA is cleaved and the resulting 63 kD carboxyl-terminal fragment binds to LF and EF. LF is a protease that is known to cleave members of the mitogen-activated protein kinase kinase (MAPKK) family(2).

Human immunodeficiency virus (HIV) is a retrovirusthat can lead to a condition in which the immune systembegins to fail, leading to opportunistic infections. HIV primarily infects vital cells in the humanimmune systemsuch as helper T cells(specifically CD4+ T cells), macrophagesand dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosisin infected cells; and thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytesthat recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunityis lost, and the body becomes progressively more susceptible to opportunistic infections. HIV was classified as a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry of the target cell, the viral RNA genomeis converted to double-stranded DNAby a virally encoded reverse transcriptasethat is present in the virus particle. This viral DNA is then integrated into the cellular DNA by a virally encoded integraseso that the genome can be transcribed. Once the virus has infected the cell, two pathways are possible: either the virus becomes latentand the infected cell continues to function, or the virus becomes active and replicates, and a large number of virus particles are liberated that can then infect other cells.

Inducible T-Cell Costimulator Ligand also known as ICOSLG, is part of the B7 family of co-stimulatory molecules related to B7-1 and B7-2. ICOSLG is a transmembrane glycoprotein with extracellular IgV and IgC domains, in addition it binds to ICOS on activated T cells. The dependent signaling of ICOSLG takes part in a proliferative response.

HBsAg is the surface antigen of the Hepatitis-B-Virus (HBV). The capsid of a virus has different surface proteins from the rest of the virus. The antigen is a protein that binds specifically on one of these surface proteins. It is commonly referred to as the Australian Antigen.

Caused by one of four closely related virus serotypes of the genus Flavivirus, family Flaviviridae, each serotype is sufficiently different that there is no cross-protection and epidemics caused by multiple serotypes (hyperendemicity) can occur. In cell culture experiments and mice Morpholino antisense oligos have shown specific activity against Dengue virus.

The protein encoded by this gene is a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. This cytokine is a main regulator of eosinopoiesis, eosinophil maturation and activation. The elevated production of this cytokine is reported to be related to asthma or hypereosinophilic syndromes. The receptor of this cytokine is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene, together with those for interleukin 4 (IL4), interleukin 13 (IL13), and CSF2, form a cytokine gene cluster on chromosome 5. This cytokine, IL4, and IL13 are found to be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31.

Listeriolysin O (aka LLO) is a hemolysin produced by Listeria monocytogenes bacteria, the pathogen responsible for causing listeriosis. The toxin may be regarded as a virulence factor, since it is crucial for the virulence of L. monocytogenes. LLO is a single polypeptide protein encoded by the hlyA gene and composed of 529 residues. LLO is a thiol-activated cholesterol-dependent pore forming toxin protein; therefore, it is activated by reducing agents and inhibited by oxidizing agents. Still, LLO differs from other thiol-activated toxins, as its cytolytic activity is maximized at a pH of 5.5. Inside the acidic phagosomes (average pH ~ 5.9) of cells that have phagocytosed L. monocytogenes, LLO is selectively activated by maximizing activity at a pH of 5.5. Following the phagosome lysis by LLO, the bacterium breaks out into the cytosol, where it is able to grow intracellularly, and the toxin has reduced activity in the more basic cytosol. Thus, LLO permits L. monocytogenes to break out from the phagosomes into the cytosol without harming the plasma membrane of the infected cell, which allows the bacteria to live intracellularly, where they are sheltered from extracellular immune system factors such as the complement system and antibodies. LLO also brings about dephosphorylation of histone H3 and deacetylation of histone H4 in the early phases of infection, before entry of L. monocytogenes into the host cell. The pore-forming activity is not implicated in causing the histone modifications. The modifications of the histones affect the down regulation of genes encoding proteins involved in the inflammatory response. Therefore, LLO may be significant in subverting the host immune response to L. monocytogenes. At its NH2-terminus it possesses a 25 residues long typical signal sequence excited during the secretion process. Moreover, in its NH2-terminus there is also a 19 amino acids PEST- like sequence that may target this toxin for degradation. The PEST-like sequence found in LLO and is considered crucial for virulence, given that mutants lacking the sequence lysed the host cell. Nevertheless, contrary to PEST's supposed role in protein degradation, evidence implies that the PEST-like sequence may control LLO production in the cytosol rather than increase degradation of LLO.

Interleukin 33 (IL-33) is a 32kDa proinflammatory cytokine that may also regulate gene transcription in producer cells. IL-33 is structurally related to IL-1, which induces helper T cells to produce type 2 cytokines and acts through the receptor IL1RL-1 (IL1 receptor-like-1), which is known also as ST2. Binding of IL-33 to this receptor activates NF-kappa-B and MAP kinases and induces in vitro Th2 cells to produce cytokines. In vivo, IL-33 induces expression of IL-4, IL-5, IL-13 and leads to severe pathological changes in mucosal organs and in vitro, it can be divided to N-terminal fragment of 12kDa and C-terminal fragment of 18kDa by cleavage of caspase-1.

AIMP1 (EMPA2 or p43) is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of the AIMP1 cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. Furthermore, AIMP1 is involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells.

The cytokine Macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. MIF has the unique property of being released from macrophages and T cells in response to physiological concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentration.

Bronchoalveolar lavage fluid from mice with experimentally induced allergic pulmonary inflammation contains a novel 9.4 kDa cysteine-rich secreted protein, RELM-alpha (FIZZ1, found in inflammatory zone). RELM-alpha is a secreted protein that has a restricted tissue distribution with highest levels in adipose tissue stroma. Murine RELM-alpha (FIZZ1) is the founding member of a new gene family including two other murine genes expressed, respectively, in intestinal crypt epithelium (RELM-beta) and white adipose tissue (Resistin), and two related human genes.
RELMalpha inhibits the differentiation of 3T3-L1 preadipocytes into adipocytes but has no effect on proliferation of 3T3-L1 preadipocytes. RELMalpha is able to form heterooligomers with resistin but not RELMbeta. Since RELMalpha is expressed by adipose tissue and it is a secreted factor, our findings suggest that RELMalpha may be involved in the control of the adipogenesis as well as in the process of muscle differentiation.
In the lung, RELM-alpha is induced by hypoxia and was renamed as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 micromol/L) inhibited HIMF-activated Akt phosphorylation. It also inhibited HIMFstimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. Further studies showed that HIMF had angiogenic and vasoconstrictive properties. HIMF increased pulmonary arterial pressure and vascular resistance. Further studies suggest that HIMF regulates apoptosis and may participate in lung alveolarization and maturation.

Insulin decreases blood glucose concentration. Insulin increases cell permeability to monosaccharides, amino acids and fatty acids. Insulin accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

Forty-two antigenic domains were identified across the hepatitis A virus (HAV) polyprotein by using a set of 237 overlapping 20-mer synthetic peptides spanning the entire HAV polyprotein. Nineteen antigenic domains were found within the structural proteins, and 22 were found within the nonstructural proteins, with 1 domain spanning the junction of VP1 and P2A proteins. Five of these domains were considered immunodominant, as judged by both the breadth and the strength of their immunoreactivity. One domain is located within the VP2 protein at position 57-90 aa. A second domain, located at position 767-842 aa, contains the C-terminal part of the VP1 protein and the entire P2A protein. A third domain, located at position 1403-1456 aa, comprises the C-terminal part of the P2C protein and the N-terminal half of the P3A protein. The fourth domain, located at position 1500-1519 aa, includes almost the entire P3B, and the last domain, located at position 1719-1764 aa, contains the C-terminal region of the P3C protein and the N-terminal region of the P3D protein. Four of the five most immunoreactive domains are derived from small HAV proteins and/or encompass protein cleavage sites separating different HAV proteins.

Overexpression of the HIF1AN is linked with tumor aggressiveness in pancreatic endocrine tumors. HIF1AN hydroxylates Notch ICD at two residues that are crucial for the function of Notch ICD as a transactivator within cells and during neurogenesis and myogenesis. HIF1AN is commonly expressed in invasive breast carcinoma. The hypoxic response and survival recommends that tumour regulation of HIF1AN is an additional important mechanism for HIF pathway activation. HIF1AN is an asparaginyl hydroxylase enzyme that controls the transcriptional activity of hypoxia-inducible factor. FIH1 is a part of the Fe2+ and 2-oxoglutarate-dependent dioxygenase superfamily, FIH1 is protein that hydoxylates a specific asparagine residue (Asn-803) within the HIF1A C-terminal transactivation domain. In normoxia, the HIF1AN-mediated hydroxylation of the HIF1? transactivation domain which results in blockage of the HIF1A-p300/CBP interaction and represses transcriptional activity of HIF1A targeted genes.

HCV is a small 50nm, enveloped, single-stranded, positive sense RNAvirus in the family Flaviviridae.
HCV has a high rate of replication with approximately one trillion particles produced each day in an infected individual. Due to lack of proofreading by the HCV RNA polymerase, the HCV has an exceptionally high mutation rate, a factor that may help it elude the host's immune response. Hepatitis C virus is classified into six genotypes(1-6) with several subtypes within each genotype. The preponderance and distribution of HCV genotypes varies globally. Genotype is clinically important in determining potential response to interferon-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to interferon-based treatment than are the other genotypes (2, 3, 5 and 6).

IL-17F having an accession number of Q96PD4 is a cytokine that shares sequence similarity with IL17. IL-17F is expressed by activated T cells, and has been shown to stimulate the production of several other cytokines, including IL6, IL8, and CSF2/GM_CSF. IL-17F inhibits the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1. IL-17F induces stromal cells to produce proinflammatory and hematopoietic cytokines. Intestinal IL17F gene expression is increased in active CD.
IL-17A & IL-17F alleles influence the susceptibility to and pathophysiological features of ulcerative colitis independently. IL-17F and MIF gene polymorphisms are significantly associated with the development of functional dyspepsia.
The initiation of IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. IL-17F induces expression of IFN-gamma-inducible protein 10 (IP-10) by activating Raf1-mitogen-activated protein kinase 1/2-extracellular-regulated kinase 1/2-p90 ribosomal S6 kinase-cyclic AMP response element-binding protein signaling pathway.

Leukemia Inhibitory Factor also called LIF is a lymphoid factor that promotes long-term maintenance of embryonic stem cells by suppressing spontaneous differentiation. Leukemia Inhibitory Factor has several functions such as cholinergic neuron differentiation, control of stem cell pluripotency, bone & fat metabolism, mitogenesis of factor dependent cell lines & promotion of megakaryocyte production in vivo. Human and mouse LIF exhibit a 78% identity in its amino acid sequence.