Microbiology and Immunology

Retroviruses WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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posonsat a new site, and most of them contain inverted

repeats at their ends. The major difference between bacterial

transposable elements and their eukaryotic counterparts is the

mechanism of transposition. Only eukaryotic genomes con-

tain a special type of transposable elements, called retro-

posons, which use reverse transcriptase to transpose through

an RNAintermediate.

Transposition may result in splicing of DNA fragments

into or out of the genome. During replicative transposition, the

transposon is first replicated giving a new copy that is trans-

ferred to a new site, with the old copy being left at the origi-

nal site. Nonreplicative transposition however describes the

movement of a transposon that is excised from a donor site,

usually generating a double, and is integrated in a new site.

The most basic transposable elements in bacteriaare

insertion sequences, which encode only for one enzyme, the

transposase. Longer bacterial transposons contain at least one

more protein-coding gene, which most frequently is an antibi-

otic resistancegene. In eukaryotes, retroposons are more

common than transposons. They are either retroviral or nonvi-

ral. Viral retroposons encode for the enzymesreverse tran-

scriptase and integrase and are flanked by long terminal

repeats (LTRs) in the same way as retroviruses. The typical

and most abundant nonviral retroposons are the short inter-

spersed elements (SINEs) and the long interspersed elements

(LINEs), which are usually repeated, many times in the mam-

malian genome. Both SINEs and LINEs lack LTRs and are

thought to transpose through a special retrotransposition

mechanism that involves transcriptionof one strand of the

retroposon into RNA. This RNA undergoes conformation

change (looping) and provides a primer for the synthesis of

single stranded cDNA. The cDNA later serve as template for

the synthesis of a double stranded DNA that is inserted in the

genome by yet unknown mechanisms.

Transposons and retroposons seem to play a role in evo-

lutionand biology by promoting rearrangement and restruc-

turing of genomes. Transposition may directly cause both

deletion and inversion mutagenesis. Furthermore, transpos-

able elements mediate the movement of host DNA sequences

to new locations, enrich the genome with identical sequences

positioned at different locations, and promote homologous

recombination. Such recombination may eventually result in

deletions, inversions, and translocations.

Transposons usually influence the expression of the

genes in proximity of their insertion sites. They have therefore

been extensively used as tools to create random insertion

mutantsin bacteria, yeastand higher eukaryotes. They are

also used in large-scale functional genomic studies. They are

valuable both during the cloningof genes and the generation

of transgenic animals.

See alsoMicrobial genetics; Transposition

RRetrovirusesETROVIRUSES

Retroviruses are virusesin which the genetic material consists

of ribonucleic acid(RNA) instead of the usual deoxyribonu-

cleic acid(DNA). Retroviruses produce an enzyme known as

reverse transcriptase that can transform RNA into DNA,

which can then be permanently integrated into the DNA of the

infected host cells.

Many genetherapy treatments and experiments use dis-

abled mouse retroviruses as a carrier (vector) to inject new

genes into the host DNA. Retroviruses are rendered safe by

adding, mutating, or deleting viral genes so that the virus can-

not reproduce after acting as a vector for the intended delivery

of new genes. Although viruses are not normally affected by

antibiotics, genes can be added to retroviruses that make them

susceptible to specific antibiotics.

As of 2002, researchers have discovered only a handful

of retroviruses that infect humans. Human immunodeficiency

virus(HIV), the virus that causes acquired immune deficiency

syndrome (AIDS), is a retrovirus. Another human retrovirus,

human T-cell leukemia virus(HTLV), was discovered three

years prior to the discovery of HIV. Both HTLV and HIV

attack human immune cells called T cells. T cells are the linch-

pin of the human immune response. When T cells are infected

by these retroviruses, the immune systemis disabled and sev-

eral serious illnesses result. HTLV causes a fatal form of can-

cer called adult T cell leukemia. HTLV infection of T cells

changes the way the T cells work in the body, causing cancer.

HIV infection of T cells, however, eventually kills T cells, ren-

dering the immune system powerless to stave off infections

from microorganisms.

Retroviruses are sphere-shaped viruses that contain a

single strand or a couple of strands of RNA. The sphere-

shaped capsule of the virus consists of various proteins. The

capsule is studded on the outside with proteins called receptor

proteins. In HIV, these receptor proteins bind to special pro-

teins on T cells called CD4 receptors. CD4 stands for cluster

of differentiation, and CD type 4 is found on specific T cells

called helper cells. The human retroviruses discovered so far

bind only to CD4 receptors, which makes their affinity for T

helper cells highly specific.

The retrovirus receptor docks with a CD4 receptor on a

T cell, and enters the T cell through the T cell membrane. Once

inside, the retrovirus begins to replicate. But because the retro-

virus’s genetic material consists of RNA, not DNA, replica-

tion is more complicated in a retrovirus than it is for a virus

that contains DNA.

In all living things, DNA is the template by which RNA

is transcribed. DNA is a double-stranded molecule that is

located within the nucleusof cells. Within the nucleus, DNA

transcribes RNA, a single-stranded nucleic acid. The RNA

leaves the nucleus through tiny pores and enters the cyto-

plasm, where it directs the synthesis of proteins. This process

has been called the “central dogma” of genetic transcription.

No life form has been found that violates this central dogma—

except retroviruses. In retroviruses, the RNA is used to tran-

scribe DNA, which is exactly opposite to the way genetic

material is transcribed in all other living things. This reversal

is why they are named retrograde, or backwards, viruses.

In addition to RNA, retroviruses contain an enzyme

called reverse transcriptase. This is the enzyme that allows the

retrovirus to make a DNA copy from RNA. Once this DNA

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