Virusmediated cytopathology changes in the biochemical properties of cells

Virus infection leads to specific changes in biochemical processes of the cell. Some viruses, such as HSV and poliovirus, specifically inhibit cellular protein synthesis. The mechanism for such inhibition is complex and differs for different viruses. Viral infection also can lead to specific inhibition of cellular mRNA synthesis. Gross inhibition of cellular macromolecular metabolism

Fig. 10.4 HSV-induced changes in the properties of actin microfilaments of a cultured monkey fibroblast. The cell was stained with a fluorescent dye that reacts with actin fibers so that they can be visualized in ultraviolet light. This technique is similar to immunofluorescence microscopy, which is discussed in Chapter 12. The left panel shows parallel arrangement of the microfibrils in the uninfected cell, while HSV infection (right panel) results in disassociation of the fibrils and diffusion of the actin throughout the cytoplasm. At the same time, the cell loses its spindle-shaped morphology and becomes rounded. The arrows indicate junctions between cells that are also rich in actin fibrils and are not disrupted by HSV infection at this time. (Courtesy of Stephen Rice.)

Uninfected cells

HSV infected cells

Uninfected cells

HSV infected cells will lead to cell death. However, there are complex and multifaceted effects of virus infection on cell function resulting from subtle changes in cellular functions that do not result in cell death, but favor virus production.

A striking example of the ability of certain DNA tumor viruses to prevent cell death long enough to allow efficient virus replication is found in viral inhibition of apoptosis. Another very important consequence of infection is, as discussed earlier, changes in the growth properties and life span of virus-infected cells. The growth rate, total number, and life span of differentiated cells are tightly controlled through the auspices of specialized tumor suppressor genes, so named because they block the formation of tumors. The interactions between viral genes and tumor suppressor genes are generally well understood in the replication of papovaviruses and adenoviruses, and are described in Chapter 16, Part IV. For the purposes of this discussion, it suffices to note that DNA-tumor viruses inhibit the tumor suppressor genes as a method to "activate" the cell for their own replication. The induction of apoptosis would interfere with the cell's ability to support virus replication. The mechanism of transformation varies between different tumor viruses, but in many cases specific virus-induced inhibition of apoptosis as well as inactivation of cellular genes actively inhibiting cell division are both important factors.

Another major effect of virus infection is interaction between the infected cell and the host's immune system. As briefly outlined in Chapter 8, Part II, and more specifically in chapters describing specific viruses (Part IV), many viruses contain genes that function to specifically inhibit the production of interferon in the infected cell. Further, certain viruses, such as HSV, can specifically inhibit major histocompatibility complex class I (MHC-I)-mediated antigen presentation at the early stages of infection. Although eventually the cell will express viral antigens as infection proceeds, this early inhibition of antigen processing can provide the virus with a vital head start in its infection.

Virus infection of cells can lead to a number of specific cellular responses that involve the expression of new cellular genes, or the increase in expression of some cellular genes. The interferon response described in Chapter 8 is a good example of this. Several techniques of modern molecular biology allow very precise identification of cellular genes induced by virus infection.

One method is termed differential display analysis and requires the use of groups of oli-gonucleotide primers, retrovirus reverse transcriptase, and the polymerase chain reaction (PCR) to generate and amplify complementary DNA copies of cellular transcripts. By comparison of the amplification patterns of products isolated from uninfected and infected cells, increases or decreases in levels of specific cellular gene transcription can be determined.

Other methods used involve microchip technology in which numerous (up to 64,000) oligonucleotide probes specific for various cellular genes are bound to a very small microarray and hybridized with PCR-amplified complementary DNA (cDNA) samples made from mRNA isolated from uninfected and infected cells and labeled with different-colored fluorescent dye. Comparison of the patterns of light emission when the microchip is scanned with a laser beam leads to identification of changes in cellular transcription. The general methodology for microchip analysis and PCR is discussed in the two following chapters.

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