by Arpita Myles
Acquired immunodeficiency syndrome or
AIDS is a global health problem that has terrified and intrigued scientists and
laypeople alike for decades. AIDS is caused by the Human Immunodeficiency
Virus, or HIV, which is transmitted through blood, semen, vaginal fluid, and
from an infected mother to her child [1]. Infection leads to failure
of the immune system, increasing susceptibility to secondary infections and
cancer, which are mostly fatal. Considerable efforts are being put into
developing prophylactic and therapeutic approaches to tackle HIV-AIDS, but there
is also interest in understanding how the disease became so wide-spread. With the
advent of the Ebola and Zika viruses in the last couple of years, there is a
renewed urgency in understanding the emergence and spread of viruses in the
past in order to prevent those in the future. The narrative surrounding the spread
of HIV has been somewhat convoluted, but a new paper in Nature by Worobey et. al,
hopes to set the record straight [2].
Humans are supposed to have acquired HIV
from African chimpanzees- presumably as a result of hunters coming in contact
with infected blood, containing a variant of the virus that had adapted to infect
humans. The earliest known case of HIV in humans was detected in 1959 in
Kinshasa, Democratic Republic of the Congo, but the specific mode of
transmission was never ascertained [3].
There has been little or no information
about how HIV spread to United States, until now. HIV incidences were first
reported in the US in 1981, leading to the recognition of AIDS [4].
Since the virus can persist for a decade or more prior to manifestation of
symptoms, it is possible that it arrived in the region long before 1981.
However, since most samples from AIDS patients were collected after this date, efforts
to establish a timeline for HIV’s entry into the states met with little
success. Now, researchers have attempted to trace the spread of HIV by
comparing genetic sequences of contemporary HIV strains with blood samples from
HIV patients dating back to the late 1970’s [2]. These samples were
initially collected for a study pertaining to Hepatitis B, but some were found
to be HIV seropositive. This is the first comprehensive genetic study of the
HIV virus in samples collected prior to 1981.
The technical accomplishment of this
work is significant as well. In order to circumvent the problems of low amounts
and extensive degradation of the viral RNA from the patient samples, they
developed a technique they call “RNA jackhammering.” In essence, a patient’s genome is broken down
into small bits and overlapping sequences of viral RNA are amplified. This
enables them to “piece together” the viral genome, which they can then subject
to phylogenetic analysis.
Using novel statistical analysis methods,
Worobey et al. reveal that the virus
had probably entered New York from Africa (Haiti) during the 1970s, whereupon
it spread to San Francisco and other regions. Upon analyzing the older samples,
the researchers found that despite bearing similarities with the Caribbean
strain, the strains from San Francisco and New York samples differed amongst
themselves. This suggests that the virus had entered the US multiple, discreet
times and then began circulating and mutating. Questions still remain regarding
the route of transmission of the virus from Haiti to New York.
The relevance of this study is
manifold. Based on the data, one can attempt to understand how pathogens spread
from one population to another and how viruses mutate and evolve to escape
natural immunity and engineered therapeutics. Their molecular and analytical
techniques can be applied to other diseases and provide valuable information
for clinicians and epidemiologists alike. Perhaps the most startling revelation
of this study is that contemporary HIV strains are more closely related to their
ancestors than to each other. This implies that information derived from
ancestral strains could lead to development of successful vaccine strategies.
Beyond the clinic and research labs,
there are societal lessons to be learned as well. Published in 1984, a study by
CDC (Center for Disease Control) researcher William Darrow and colleagues
traced the initial spread of HIV in the US to Gaétan Dugas- a French Canadian air steward. Examination of Dugas’s
case provided evidence linking HIV transmission with sexual activity. Researchers
labeled Dugas as “Patient O”, as in “Out of California” [5]. This was misinterpreted as “Patient Zero” by the media- a
term still used in the context of other epidemics like flu and Ebola. The dark
side of this story is that Dugas was demonized in the public domain as the one who brought HIV to the US.
As our understanding of the disease and its spread broadened, scientists and
historians began to discredit the notion that Dugas played a significant role.
However, scientific facts were buried beneath layers of sensationalism and
hearsay and the stigma remained.
Now, with the new information brought to
light by Worobey’s group, Dugas’s name has been cleared. Phylogenetic analysis
of Dugas’s strain of HIV was sufficiently different from the ancestral ones,
negating the possibility that he initiated the epidemic.
The saga in its entirety highlights the
moral dilemma of epidemiological studies and the extent to which the findings
should be made public. Biological systems are complicated, and while narrowing
down origin of a disease has significance clinical relevance, we often fail to
consider collateral damage. The tale of tracking the spread of HIV is a
cautionary one; scientific and social efforts should be focused more on
resolution and management, rather than on vilifying unsuspecting individuals
for “causing” an outbreak.
References:
1. Maartens
G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and
prevention. Lancet. 2014 Jul 19;384(9939):258-71.
2. Worobey
M, Watts TD, McKay RA et al., 1970s and 'Patient 0' HIV-1 genomes illuminate
early HIV/AIDS history in North America. Nature. 2016 Oct 26. doi:
10.1038/nature19827.
3. Faria
NR, Rambaut A et al., HIV epidemiology. The early spread and epidemic ignition
of HIV-1 in human populations. Science. 2014 Oct 3;346(6205):56-61.
4. Centers
for Disease Control (CDC). Pneumocystis pneumonia--Los Angeles. MMWR Morb
Mortal Wkly Rep. 1981 Jun 5;30(21):250-2.
5. McKay
RA. “Patient Zero”: The Absence of a Patient’s View of the Early North American
AIDS Epidemic. Bull Hist Med. 2014 Spring: 161-194.