Host cell mechanism

While the poly (A) sequences do seem to be involved in the transport of mRNA s from the nucleus, this does not seem to be the sole function of the poly (A) tract for example, adenovirus DNA appears to lack a DNA sequence complementary to poly (A) but replicates in the nucleus of the mammalian cell and appears to have a poly (A) tract added to the viral mRNA by host-cell mechanisms for transport of the adenovirus mRNA to the cytoplasm (Philipson et ah, 1971). As with cellular messages, cordycepin blocks both the labeling of the poly (A) tracts and the appearance of adenovirus-specific RNA in the cytoplasm of infected cells (Philipson et ah, 1971). In contrast, vaccinia virus replicates exclusively in the cytoplasm of cells it infects and still contains poly(A) sequences (Kates, 1970). Since no role in transport is involved here, it suggests that some mRNAs may require a poly (A) sequence for proper translation. Further, not all mammalian mRNAs contain poly (A) and still are transported to the cytoplasm for translation. Specifically, the 9 S histone message isolated by Adesnik and Darnell (1972) from HeLa cells lacks any detectable poly (A) sequence of any significant length. These workers have also shown that the exit time of the histone mRNA molecule from the nucleus is shorter than that of other messenger RNA s. 

The antiviral mechanism of action of acyclovir has been reviewed (72). Acyclovir is converted to the monophosphate in herpes vims-infected cells (but only to a limited extent in uninfected cells) by viral-induced thymidine kinase. It is then further phosphorylated by host cell guanosine monophosphate (GMP) kinase to acyclovir diphosphate [66341 -17-1], which in turn is phosphorylated to the triphosphate by unidentified cellular en2ymes. Acyclovir triphosphate [66341 -18-2] inhibits HSV-1 viral DNA polymerase but not cellular DNA polymerase. As a result, acyclovir is 300 to 3000 times more toxic to herpes vimses in an HSV-infected cell than to the cell itself. Studies have shown that a once-daily dose of acyclovir is effective in prevention of recurrent HSV-2 genital herpes (1). HCMV, on the other hand, is relatively uninhibited by acyclovir. 

The selective stimulation of these cells is of importance because they are the most active effector cells in host defense mechanisms against bacterial and viral infections. 

Cooper M. R. (1983). The mechanisms and significance of enzymatic degradation of host cell walls by parasites. In Callow J. A., ed. Biochemical Plant Pathology. John Wiley Sons Ltd., 101-135. 

The first is glycosaminoglycan, a compound produced by the body that coats the epithelial cells of the bladder. This compound essentially separates the bladder from the urine by forming a protective layer against bacterial adhesion.14 A second compound known as Tamm-Horsfall protein is secreted into the urine, and prevents E. coli from binding to receptors present on the surface of the bladder. Other factors implicated in contributing to host defense mechanisms include immunoglobulins, specifically IgA, and lactobacilli, bacteria that are part of the normal vaginal flora.13,15... 

Finally, during budding, HIV-1 may also incorporate into its membrane envelope a variety of different molecules, including proteins that may subsequently interact with their counterparts on the host cell membrane (reviewed in ref. 192), resulting in intracellular signaling and facilitation of virus fusion (193,194). However, the incorporation of cell membrane-derived molecules does not appear to be an absolute requirement for virus entry (195), indicating the leading role of CD4 and the coreceptor for any such mechanism. However, this phenomenon may account for lower levels of inhibition when the effects of mutant CD4 and/or chemokine receptor are studied. 

The nonnucleoside reverse transcriptase inhibitors (NNRTIs), used in the treatment of AIDS, provide interesting examples of clinically relevant noncompetitive inhibitors. The causative agent of AIDS, HIV, belongs to a virus family that relies on an RNA-based genetic system. Replication of the vims requires reverse transcription of the viral genomic RNA into DNA, which is then incorporated into the genome of the infected host cell. Reverse transcription is catalyzed by a virally encoded nucleic acid polymerase, known as reverse transcriptase (RT). This enzyme is critical for viral replication inhibition of HIV RT is therefore an effective mechanism for abrogating infection in patients. 

Penetration The means by which the vims penetrates into the cell depends on the nature of the host cell, especially on its surface stmctures. Cells with cell walls, such as bacteria, are infected in a different manner from animal cells, which lack a cell wall. The most complicated penetration mechanisms have been found in viruses that infect bacteria. The bacteriophage T4, which infects E. coli, can be used as an example. 

Virus infection obviously upsets the regulatory mechanisms of the host, since there is a marked overproduction of nucleic acid and protein in the infected cell. In some cases, virus infection causes a complete shutdown of host macromolecular synthesis while in other cases host synthesis proceeds concurrently with virus synthesis. In either case, the regulation of virus synthesis is under the control of the virus rather than the host. There are several elements of this control which are similar to the host regulatory mechanisms, but there are also some uniquely viral regulatory mechanisms. We discuss various regulatory mechanisms when we consider the individual viruses later in this chapter. 

Four fundamental changes induced in host cells will be discussed initially (i) infection-induced cell cycle re-entry (ii) suspension of host cells in apparent G2/M (iii) repression of host muscle gene expression and (iv) further induction of the infected cell phenotype. A clear understanding of these fundamental changes induced by the infection is critical in elucidating the cellular mechanisms involved and, possibly, the host regulatory factors that are interfered with by parasite products. 

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