Epidemiology and HIV’s Physical Properties

OCT.19 '95 7:32AM 310-446-1664 LAYME @ UCLA. [phone] P.3
COMMENTARY
sequenced all the structural and regulatory proteins, measured their enzymatic activities, determined
their crystallographic structures, and studied their undermining influences on the immune system.
Nevertheless, we have yet to fathom how all constituents of the virus work together to affect
person-to-person transmissibility. Studying certain "physical" properties of HIV (such as
infectious fractions, spontaneous decay rates, and viral reproductive numbers) may provide us
with an understanding of the mechanisms governing transmissibility. As explained below, this
wilt require a somewhat new approach to the problem in combination with a concerted
interdisciplinary effort.
Current limitations
The RNA genome within HIV mutates very rapidly, primarily due to the error-prone activity of
reverse transcriptase-s. This enzyme produces nearly one RNA substitution per 3000 nucleotides,
which means that each newly transcribed virus contains several mutations in its 10,000-base
genome. The high mutation rate has produced countless numbers of HIV variants and, as time
passes, it is feasible that more transmissible viruses may appear in concert with accelerating
epidemics. This may help to explain the explosive IlIV epidemic in Thailand.
A burst of viral reproduction occurs when individuals first become infected with HIV.
Quantitative HIV-RNA PCR assays reveal that cell-free virus in blood reaches concentrations as
high as 106 - 107 particles per m16 and concentrations in lymphoid tissues are ten-fold greater7ts.
Within weeks following this chain reaction-like event, humoral and cellular immune responses
develop which control the acute viremia. Viral loads soon reach man equilibrium where clearance by
the immune system matches the production of new viral particles, with measurable concentrations
in blood ranging from 102 - 105 cell-free particles per ml9.1. After several years, however, the
stalemate between opposing forces subsides and individuals progress to symptomatic HIV
infection. Antiviral drugs (such as reverse transcriptase and protease inhibitors) offer only
temporary benefits duo to the rapid selection of drug-resistant variants. As the immune system
loses its capacity to clear escalating infection, viral loads climb to concentrations above 105

particles per ml and even more pathogenic viruses may emerge that reproduce in greater
numbersit.
Studying the RNA message within HIV has resulted in th cataloguing of thousands of HIV
2