Immune Evasion by Parasites Causing Tropical Diseases 
ahead" of the host immune defenses. We are ex- 
amining the events at the DNA and RNA level that 
are responsible for this antigenic variation. 
We know that the trypanosome genome con- 
tains about 1,000 different genes encoding anti- 
genically distinct VSGs. Usually one, and only 
one, of these VSG genes is expressed at a time. 
Rearrangements and duplications of these genes 
are partly responsible for the selection of the VSG 
gene to be transcribed and for the switch event 
itself. 
The rearrangements maneuver specific VSG 
genes into and out of special chromosomal loca- 
tions, called expression sites, where transcrip- 
tion occurs. These expression sites are always ad- 
jacent to the ends of the chromosomes — the 
chromosomal telomeres. The process is compli- 
cated by the fact that several, and perhaps many, 
potential expression sites exist in the genome, 
yet only one is normally activated at any time. 
Our goal is to understand this activation mecha- 
nism at the molecular level. In one project we 
have identified a protein that specifically binds to 
a region upstream of a VSG gene in an expression 
site activated during the final developmental 
stage of the parasite in the tsetse fly, i.e., the 
metacyclic stage. This protein may contribute to 
the developmental regulation of that VSG gene's 
transcription. In another project we have de- 
tected a high rate of mutation in the telomere- 
linked VSG genes, which may increase the effec- 
tiveness of antigenic variation still further. A third 
project involves characterization of a group of 
small chromosomes that are unique to African 
trypanosomes and contain many of the VSG genes 
destined for sequential expression. 
Onchocerciasis 
Onchocerca volvulus is a filarial nematode 
that causes onchocerciasis, or river blindness, in 
Africa and Latin America. Female O. volvulus 
worms grow to 50 cm in length and reside 
throughout the body within nodules. Here they 
produce thousands of microfilariae each day that 
migrate throughout the body and enter the eyes, 
where they produce lesions that can lead to 
blindness. It is not known how any of the develop- 
mental stages of the parasite in the host evade the 
immune response. The parasites are difficult to 
study in the laboratory, because there is no good 
experimental animal model; they infect only hu- 
mans and chimpanzees. We have constructed 
cDNA expression libraries of the mRNAs from the 
infective L3 stage larvae of the parasite, and from 
the L4 stage larvae that quickly develop after in- 
fection, and are using specific cDNA clones to 
overproduce parasite antigens from both stages 
that are recognized by antisera from onchocercia- 
sis patients. This approach has revealed several 
proteins that are unique to the parasite and may 
be valuable for improved diagnosis, treatment, 
and prevention of the disease. 
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