Viruses infection cycle

Viruses, like all pathogens, show host specificity, usually infecting only one or a restricted range of host species. The initial basis of specificity is the ability of the virus particle to attach to the host cell. If the amount of infectious virus is measured over a period of time in the host, it is seen to fall, after an initial lag period, remain low for a period of time, and then rise to even higher levels. The period during which the amount of virus is low is referred to as the eclipse period. The virus infection cycle can be divided into several events. 

Viruses borrow heavily on the host enzymatic machinery to obtain energy for synthesis, as well as for replication, transcription, and translation. The virus infective cycle is strongly irreversible. Virus infection is followed by the gradual turning on of viral genes. Viral enzymes are the first viral gene products in late infection, the virus structural proteins are favored. The irreversible lytic cycle of the virus is directed by a cascade of controls. 

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

FIGURE 84-1. Life cycle of HIV and targets for antiretroviral drugs. (From Fletcher CV, Kakuda TN. Human immunodeficiency virus infection. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 2258, with permission.)... 

Viruses lack independent metabolism. They multiply only inside living cells, using the host cell metabolic machinery. Some virus particles do contain enzymes, however, that are under the genetic control of the virus genome. Such enzymes are only produced during the infection cycle. 

Nearly 40 million people are infected with the human immunodeficiency virus (HIV). Over half of those infected reside in sub-Saharan Africa. Worldwide during 2004, it is estimated that nearly 14,000 people a day were infected. Human immunodeficiency virus type 1 is the primary etiological source for the acquired immunodeficiency syndrome (AIDS). Fortunately, people infected with HIV are leading longer and more productive lives due to the availability of more effective therapies. Better medicines have evolved due to the efforts of scientists worldwide who find targets and compounds that inhibit the virus life-cycle. The current treatment for HIV infection is via a drug cocktail that usually includes a protease inhibitor (PI), a nucleoside reverse transcriptase inhibitor (NRTI), and a non-nucleoside reverse transcriptase inhibitor (NNRTI). 

Zanamivir (2) is a potent competitive inhibitor of viral neuraminidase glycoprotein, which is essential in the infective cycle of both influenza A and B viruses. It inhibits a wide range of influenza A and B types in vitro as well as in vivo. The concentrations of inhibiting in vitro plaque formation of influenza A and B virus by 50% in Madin-Darby canine kidney (MDCK) cells were 0.004-0.014 p.mol/L in laboratory-passaged strains, and 0.002-16 p.mol/L in assays of clinical isolates. Due to its low bioavailability, it is delivered by inhalation via the Diskhaler , 10 mg twice daily, or intranasally 2-4 times daily for 5 days. After an intravenous dose of 1 -16 mg, the median elimination half-life was ti/2 = 7 h, the volume of distribution at steady state was Vdss = 16 L, and 90% of the dose was excreted unchanged in the urine. After intranasal and inhaled (dry powder) administration, maximum serum concentrations occurred within 2h and the terminal phase half-lives were 3.4 and 2.9 h, respectively. The bioavailabilities were 10 and 25%, respectively, and 20% after inhalation of zanamivir (2) by nebulizer. 

Success in treating AIDS may depend upon better understanding of the complex life cycle of HIV-1,722,730,735 w -,jc -, js summarized in Fig. 28-27. The cycle begins with the binding of the virion envelope protein to the immunoglobulin-like surface protein CD4, which is found principally on the type T4 helper T cells (Chapter 31). Binding of CD4 to the HIV envelope proteins appears to activate the T cells to enter the cell cycle and to take up and integrate the virus. The virus infection destroys these CD4+ lymphocytes with a half-life of less than two days.735... 

Abstract. TPA and RA have significant effects on glycolipid and glycoprotein biosynthetic enzymes in several cultured cell systems. This suggests that these compounds as well as other "tumor promoters" will be useful in further studies on the regulation and control of glycoconjugate metabolism (metabolic perturbants). Butyrate, TPA and RA appear to exert their effects at different points in the cell cycle. These results could mean that tumor promotion, differentiation and virus infection occur at discrete points in the cell cycle. Membrane glycoconjugates may participate in these processes in a dynamic time-dependent way. 

The infection cycle is shown in Figure 19.2. When the polyhedra are dispersed in the environment, the viral particles inside them (ODVs) are deposited on the plant leaves. When the caterpillars feed on the virus-contaminated foliage, they ingest the polyhedra. The alkaline environment in the caterpillar medium intestine causes breakdown of the polyhedra and the viral particles are released from the polyhedra. The infection of the cells occurs via a receptor-mediated fusion process. Once in the cytoplasm, the nucleocapsids without membrane are transported to the nucleus of the cell, where gene expression and genome replication begins. 

Detailed laboratory studies showed that the total length of the lytic growth cycles of the Phaeocystis viruses infecting exponentially growing host cells ranged between 25 and 50 h (Jacobsen et al. 1996 Baudoux and Brussaard 2005). For PpV the latent period, the time period from infection until the first increase in the abundance of extracellular free viruses, was around 12-18 h (Jacobsen et al. 1996). The study by Baudoux and Brussaard (2005) showed three different latent periods for the various PgV isolates in culture, i.e., 10,12 and 16 h (Fig. 3). These periods match the range of latent periods for all characterized phytoplankton viruses so far, and are somewhat... 

During its infection cycle, for a productive infection to occur, the virus must release the encapsidated genome at an appropriate location inside the host cell. The genome release is often associated with the disassembly... 

Despite some uncertainties as to the overall role of PVR in vivo, several studies link the importance of this receptor to the virus life cycle. Kaplan et al. showed that exposure of poliovirus to soluble PVR converted the 160S particle to the 135S form and that this was associated with reduced infectivity (Kaplan et al., 1990). Other investigators showed that antibody-coated poliovirus was unable to enter nonpermissive GHO cells bearing Fc receptors, whereas, in contrast, foot-and-mouth disease virus (FMDV) was able to utilize this alternative entry pathway (Mason et al, 1994). Thus, PVR selectively mediates conformational changes in the poliovirus particle that are associated with cell entry and confers virus infection of cultured cells. Further studies will be necessary to explain why the broad distribution of this receptor does not allow virus replication in many cell types in vivo. 

Figure 7-3 a The function of interferon. When a virus infects a host cell, the cell expresses interferon. Interferon activates natural killer cells, causing killing of the infected host cells and elimination of the reservoir of infection. At the same time, interferon induces an antiviral state in neighboring cells, effectively breaking the cycle of infection. 

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