Viral DNA Is Integrated into the Host Cell Genome in Some Nonlytic Viral Growth Cycles

Some bacterial viruses, called temperate phages, can establish a nonlytic association with their host cells that does not kill the cell. For example, when \ bacteriophage infects E. coli, the viral DNA may be integrated into the host-cell chromosome rather than being replicated. The integrated viral DNA, called a prophage, is replicated as part of the cell's DNA from one host-cell generation to the next. This phenomenon is referred to as lysogeny. Under certain conditions, the prophage DNA is activated, leading to its excision from the host-cell chromosome, entrance into the lytic cycle, and subsequent production and release of progeny virions.

Genomic ssRNA

Reverse transcriptase

Retrovirus proteins

Host-cell chromosomal DNA

Genomic ssRNA

Reverse transcriptase

Retrovirus proteins

Host-cell chromosomal DNA

▲ FIGURE 4-43 Retroviral life cycle. Retroviruses have a genome of two identical copies of single-stranded RNA and an outer envelope. Step D: After viral glycoproteins in the envelope interact with a specific host-cell membrane protein, the retroviral envelope fuses directly with the plasma membrane, allowing entry of the nucleocapsid into the cytoplasm of the cell. Step 2 Viral reverse transcriptase and other proteins copy the viral ssRNA genome into a double-stranded DNA. Step B: The viral dsDNA is transported into the nucleus and integrated into one of many possible sites in the host-cell chromosomal DNA. For simplicity, only one host-cell chromosome is depicted. Step 4 The integrated viral DNA (provirus) is transcribed by the host-cell RNA polymerase, generating mRNAs (dark red) and genomic RNA molecules (bright red). The host-cell machinery translates the viral mRNAs into glycoproteins and nucleocapsid proteins. Step 15: Progeny virions then assemble and are released by budding as illustrated in Figure 4-41.

The genomes of a number of animal viruses also can integrate into the host-cell genome. Probably the most important are the retroviruses, which are enveloped viruses with a genome consisting of two identical strands of RNA. These viruses are known as retroviruses because their RNA genome acts as a template for formation of a DNA molecule—the opposite flow of genetic information compared with the more common transcription of DNA into RNA. In the retroviral life cycle (Figure 4-43), a viral enzyme called reverse transcriptase initially copies the viral RNA genome into single-stranded DNA complementary to the virion RNA; the same enzyme then catalyzes synthesis of a complementary DNA strand. (This complex reaction is detailed in Chapter 10 when we consider closely related intracellular parasites called retrotransposons.) The resulting double-stranded DNA is integrated into the chromosomal DNA of the infected cell. Finally, the integrated DNA, called a provirus, is transcribed by the cell's own machinery into RNA, which either is translated into viral proteins or is packaged within virion coat proteins to form progeny virions that are released by budding from the host-cell membrane. Because most retroviruses do not kill their host cells, infected cells can replicate, pro ducing daughter cells with integrated proviral DNA. These daughter cells continue to transcribe the proviral DNA and bud progeny virions.

Some retroviruses contain cancer-causing genes (oncogenes), and cells infected by such retroviruses are oncogenically transformed into tumor cells. Studies of oncogenic retroviruses (mostly viruses of birds and mice) have revealed a great deal about the processes that lead to transformation of a normal cell into a cancer cell (Chapter 23).

Among the known human retroviruses are human T-cell lymphotrophic virus (HTLV), which causes a form of leukemia, and human immunodeficiency virus (HIV), which causes acquired immune deficiency syndrome (AIDS). Both of these viruses can infect only specific cell types, primarily certain cells of the immune system and, in the case of HIV, some central nervous system neurons and glial cells. Only these cells have cell-surface receptors that interact with viral envelope proteins, accounting for the host-cell specificity of these viruses. Unlike most other retroviruses, HIV eventually kills its host cells. The eventual death of large numbers of immune-system cells results in the defective immune response characteristic of AIDS.

Some DNA viruses also can integrate into a host-cell chromosome. One example is the human papillomaviruses (HPVs), which most commonly cause warts and other benign skin lesions. The genomes of certain HPV serotypes, however, occasionally integrate into the chromosomal DNA of infected cervical epithelial cells, initiating development of cervical cancer. Routine Pap smears can detect cells in the early stages of the transformation process initiated by HPV integration, permitting effective treatment. I

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment