Singlestranded DNA bacteriophage OX174 packages its genes very compactly

The gene packaging of bacteriophage OX174 suggests that genomic size compression offers distinct advantages in the prokaryotic world, also. This icosahedral virus has a structure very similar to that of adenovirus, but with shorter fibers. It contains a circular ssDNA genome approximately 3.4 kb long. Upon infection of a bacterial cell, the ssDNA genome is converted into dsDNA. This has been termed the replicative intermediate or replicative form (RF), but is quite unlike the complex ribonucleoprotein complex with this name seen in the replication of ssRNA viruses.

Viral-encoded mRNA expression, protein synthesis, and genome replication occur following patterns that are generally simple examples of the more complex replication programs of DNA-containing bacteriophages described in Chapter 18. A striking demonstration of the extent this virus has gone to compress its genome comes from examination of its genetic map, shown in Fig. 16.10. The virus encodes nine distinct genes, but where one might expect about 200—300 bases of the DNA sequence to contain nonprotein information, only 36 bases (<1%) of the genome are free of translational reading frames. This arrangement means that all transcriptional control sequences are contained within translational reading frames.

The start and stop signals for translation of individual neighboring ORFs often overlap. Further, two genes are completely contained within the translational reading frames of other, larger ones. This configuration is accomplished by having the translational frames in different phases (outlined in Chapter 22, Part V). While such overlapping genes are found in many viruses, including even the largest ones, such as herpesviruses and poxviruses, OX174 has taken this tendency to an extreme.

Such compactness provides some useful advantage to this bacteriophage, but as with all dynamic systems, there is a price. In a viral genome with such overlaps, one base change in a region of overlapping genes can affect two rather than one gene function. For this reason, more mutations would be expected to be lethal than is generally seen in viral genomes. This is indeed the case with OX174, whose sequence is more strongly conserved during replication than is the case with other DNA viruses, and generation of mutations in this virus for genetic analysis is a laborious task.

Overlapping genes probably result in the virus being less adaptable to host and other changes in its natural environment. This conservatism could have a negative survival value in the pro-karyotic world, but the survival of the virus is clear evidence that deleterious effects are compensated by the efficiency of gene packaging.

Bacteriophage

VPF (capsid protein)

VPH (minor spike)

VPG (major spike)

Bacteriophage

E stop

D stop

GAGTGATGTAATGTCT —

C stop

J start

ATCATGAGTC —

D start

A ! C ID;

E J 1

A stop

■•AAAATGAGAA

C start

Morphogenesis

Fig. 16.10 The capsid structure and compressed genome of bacteriophage OX174. The capsid is made up of three proteins: major capsid, major spike, and minor spike. In all, a total of 10 genes are compressed into 3.4 kb of ssDNA! This is accomplished by very short intergenic regions, and two completely overlapping genes. The functions of the proteins encoded by these genes are listed.

DNA replication

Host DNA synthesis shutoff

DNA replication viral strand synthesis

Morphogenesis

Host DNA synthesis shutoff

Capsid assembly Core protein

Capsid protein

Minor spike protein

Major spike protein

Minor spike protein

Major spike protein

Capsid assembly Core protein

Capsid protein

Case study: JC virus

Clinical presentation/case history: A 42-year-old male with AIDS (CD4 count = 128) is taken to the emergency room by his sister due to concerns over dramatic personality and mood changes. Upon admission he was incoherent and confused. A history provided by his sister indicated that his mental status changed state about 6 weeks prior. He had complained that his face hurt, and he demonstrated right arm and leg weakness and slurring of his speech. The patient had no headache, neck stiffness, or fever. The attending physician ordered blood work, as well as a CT scan (x-ray).

Diagnosis: The attending physician was concerned about the evidence of CNS deficits and suspected either an HIV encephalopathy or an AIDS-related infection of the brain. The CT scan of the head had been ordered to look for evidence of lesions in the brain. The CT showed a left temporoparietal cerebral edema (area of inflammation). This indicated a zone of pathology likely caused by an AIDS-related infection. Serology did not provide useful

Continued information for diagnosis. Because a number of viruses (and fungi) can cause lesions in the brains of AIDS patients, a brain biopsy of the lesion was ordered and PCR analysis identified JC virus DNA. This suggested the likely etiology was progressive multifocal leukoencephalopathy (PML), which is caused by a reactivation of latent JC virus that is present in some B-lymphocytes and these can cross the blood-brain barrier. Once there, they can form a focus of active infection, and result in sometimes severe cognitive deficits.

Treatment: There is no specific treatment for JC virus infection, or PML. However, the underlying cause of this infection is the ongoing HIV infection in this patient as indicated by his low CD4 count. The patient was put on HAART therapy to control his HIV, and in several weeks his CD4 count showed some recovery and the PML caused by the JC virus infection resolved

Disease notes: JC virus is a polyomavirus that is usually acquired as a subclinical infection in childhood. The virus initially infects the tonsils and then spreads through the blood where it infects the kidneys and becomes latent in the renal epithelium. JC virus has also been shown to be latent in the CNS, bone marrow, and peripheral blood cells. Greater than 80% of adults have antibodies to JC virus, and this infection normally causes no clinical problems except in the immunocompromised (and especially patients with AIDS).

Was this article helpful?

0 0
How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment