Viral proliferation

As opposed to the development of vaccines that produce antibodies, the development of T-cell vaccines is a novel concept. These vaccines are designed to induce primarily T-cell responses that will control the viral proliferation and viral levels during the early stages of infection and will delay the disease progression. These vaccines will not prevent infection but will inhibit HIV levels and protect uninfected memory CD4+ T cells. It is expected that HIV-infected patients receiving this vaccine may remain disease-free for a prolonged period of time. A number of current HIV vaccine trials have focused on CD8+ cell-mediated products that... 

These drugs are peptidyl analogs that reversibly inhibit the proteinase that is essential for the final step of viral proliferation. Protease inhibitors have revolutionized HIV therapy, reducing infections by opportunistic organisms, and prolonging and improving the lives of most patients. 

HBeAg—Correlates with viral proliferation and infectivity. D. Amebic Liver Abscesses... 

A number of plant extracts and pure compounds isolated from natural products were tested for anti-HBV activity utilizing HepG2.2.15 cells. Two parameters indicative of viral proliferation were evaluated the inhibition of secretion of HBV/HBsAg into the medium of the cultured cells and the reduction of intracellular extrachromosomal HBV DNA. Since ddC is known to inhibit HBV replication (209, 213, 254, 255), it was evaluated along with the test materials (0.5% v/v) as a positive control. The results obtained with 84 plant extracts and 57 pure compounds are summarized in Table 2. 

Interferons (IFN), cytokines that display antiproliferative, antitumor, antiviral, and immunomodulatory properties. They regulate somatic cell growth, division, and apoptosis. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway. IFN are glycoproteins secreted by virus-infected vertebrate cells preventing viral proliferation, largely by inhibition of protein synthesis in other infected cells. Three families of IFN have been characterized (a) IFN-a or leukocyte... 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

Regulate cellular response to viral infeetions and eaneer proliferation... 

Viral vaccines present problems of safety testing far more complex than those experienced with bacterial vaccines. With killed viral vaccines the potential hazards are those due to incomplete virus inactivation and the consequent presence of residual live virus in the preparation. The tests used to detect such live virus consist of the inoculation of susceptible tissue cultures and of susceptible animals. The cultures are examined for cytopathic effects and the animals for symptoms of disease and histological evidence of infection at autopsy. This test is of particular importance in inactivated poliomyelitis vaccine, the vaccine being injected intraspinally into monkeys. At autopsy, sections of brain and spinal cord are examined microscopically for the histological lesions indicative of proliferating poliovirus. 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

This approach is not restricted to bacterial or viral cells. Mammalian cells under highly proliferating conditions can be cultured at increasing exposure to a compound in attempts to create resistant mutants. Alternatively, one can sometimes use a structural biology approach to predict amino acid changes that would abrogate inhibitor affinity from study of enzyme-inhibitor complex crystal structures. If the recombinant mutant enzyme displays the diminished inhibitor potency expected, one can then devise ways of expressing the mutant enzyme in a cell type of interest and look to see if the cellular phenotype is likewise abolished by the mutation. 

Malignant Reed-Sternberg cells overexpress nuclear factor-K B, which is associated with cell proliferation and anti-apoptotic signals. Infections with viral and bacterial pathogens upregulate nuclear factor-K B. Epstein-Barr virus is found in many, but not all, HL tumors. 

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