Microbiology and Immunology

Latent viruses and diseases WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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species of experimental animals, including rabbits, guinea

pigs, mice, and monkeys. Only the monkeys contracted the

disease. Landsteiner reported the results of the experiment,

conducted with Erwin Popper, an assistant at the Wilhelmina

Hospital.

Scientists had accepted that polio was caused by a

microorganism, but previous experiments by other researchers

had failed to isolate a causative agent, which was presumed to

be a bacterium. Because monkeys were hard to come by in

Vienna, Landsteiner went to Paris to collaborate with a

Romanian bacteriologist, Constantin Levaditi of the Pasteur

Institute. Working together, the two were able to trace

poliomyelitis to a virus, describe the manner of its transmission,

time its incubation phase, and show how it could be neutralized

in the laboratory when mixed with the serum of a convalescing

patient. In 1912, Landsteiner proposed that the development of

a vaccine against poliomyelitis might prove difficult but was

certainly possible. The first successful polio vaccine, developed

by Jonas Salk, wasn’t administered until 1955.

Landsteiner accepted a position as chief dissector in a

small Catholic hospital in The Hague, Netherlands where he

performed routine laboratory tests on urine and blood from

1919 to 1922. During this time he began working on the con-

cept of haptens, small molecular weight chemicals such as fats

or sugars that determine the specificity of antigen-antibody

reactions when combined with a protein carrier. He combined

haptens of known structure with well-characterized proteins

such as albumin, and showed that small changes in the hapten

could affect antibodyproduction. He developed methods to

show that it is possible to sensitize animals to chemicals that

cause contact dermatitis (inflammationof the skin) in humans,

demonstrating that contact dermatitis is caused by an antigen-

antibody reaction. This work launched Landsteiner into a

study of the phenomenon of allergic reactions.

In 1922, Landsteiner accepted a position at the

Rockefeller Institute in New York. Throughout the 1920s

Landsteiner worked on the problems of immunity and allergy.

He discovered new blood groups: M, N, and P, refining the

work he had begun 20 years before. Soon after Landsteiner

and his collaborator, Philip Levine, published the work in

1927, the types began to be used in paternity suits.

In 1929, Landsteiner became a United States citizen. He

won the Nobel Prize for medicine in 1930 for identifying the

human blood types. In his Nobel lecture, Landsteiner gave an

account of his work on individual differences in human blood,

describing the differences in blood between different species

and among individuals of the same species. This theory is

accepted as fact today but was at odds with prevailing thought

when Landsteiner began his work. In 1936, Landsteiner

summed up his life’s work in what was to become a medical

classic: Die Spezifität der serologischen Reaktionen, which

was later revised and published in English, under the title The

Specificity of Serological Reactions.

Landsteiner retired in 1939, at the age of seventy-one,

but continued working in immunology. With Levine and

Alexander Wiener he discovered another blood factor, labeled

the Rh factor, for Rhesus monkeys, in which the factor was

first discovered. The Rh factor was shown to be responsible

for the infant disease, erythroblastosis fetalis that occurs when

mother and fetus have incompatible blood types and the fetus

is injured by the mother’s antibodies. Landsteiner died in

1943, at the age of 75.

See alsoAntibody and antigen; Antibody-antigen, biochemi-

cal and molecular reactions; Blood agar, hemolysis, and

hemolytic reactions; History of immunology; Rh and Rh

incompatibility

LLatent viruses and diseasesATENT VIRUSES AND DISEASES

Latent virusesare those viruses that can incorporate their

genetic material into the genetic material of the infected host

cell. Because the viral genetic material can then be replicated

along with the host material, the virus becomes effectively

“silent” with respect to detection by the host. Latent viruses

usually contain the information necessary to reverse the latent

state. The viral genetic material can leave the host genome to

begin the manufacture of new virus particles.

The molecular process by which a virus becomes latent

has been explored most fully in the bacteriophagedesignated

lambda. The lysogenic process is complex and involves the

interplay between several proteins that influence the tran-

scriptionof genes that either maintain the latent state or begin

the so-called lytic process, where the manufacture of new

virus begins.

Bacteriophage lambda is not associated with disease.

However, other viruses that can establish a latent relationship

with the host are capable of causing disease. Examples of

viruses include the HerpesSimplex Virus 1 (also dubbed HSV

1) and retroviruses. The latter group of viruses includes the

Human Immunodeficiency Viruses(HIVs) that are the most

likely cause of acquired immunodeficiency syndrome (AIDS).

In the case of HSV 1, the virus can become latent early

in life, when many people are infected with the virus. The

virus infects the mucous membranes located around the

mouth. From this location the virus spreads to a region of cer-

tain nerve cells called the ganglion. It is here that the viral

genetic material (deoxyribonucleic acid, or DNA) integrates

into the host genetic material. The period of latency can span

decades. Then, if the host is stressed such that the survival of

the infected cells is in peril, the viral DNA is activated. The

new virus particles migrate back to the mucous membranes of

the mouth, where they erupt as “cold sores”. A form of the

reactivated herpes virus that is known as Herpes Zoster causes

the malady of shingles. The painful sores associated with

shingles can appear all over the body.

The re-emergence of HSV 1 later in life does qualify as

a disease. However, it has been argued that the near universal

prevalence of the latent form of the viral DNA in people

worldwide qualifies HSV as being part of the normal micro-

bial makeup of humans. Others argue that even the latent HSV

state qualifies as an infection, albeit an infection that displays

no symptoms and is essentially harmless to the host.

Other examples of a latent virus include the HIVs. The

latent form of HIVis particularly insidious from the point of

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