In a continuing series of answering the question “What
does a veterinarian do?” we focus this issue on three
researchers at Penn Vet who are examining big-picture
issues with the aim to find solutions for both human kind
and animal kind. While two of our faculty members featured
are not trained as veterinarians, their work speaks to the role
of the veterinary school – and illustrates how Penn Vet is
uniquely positioned to address such public health issues.
Rabies: A Model Virus
Ronald N. Harty, PhD, associate professor of microbiology,
takes rabies seriously. Very seriously.
It’s in his lab where he and his team work to better
understand the virus, focusing on its individual proteins, with
the ultimate goal of intercepting its budding activities.
While lab workers don’t work with the live virus –
instead they use Vesicular Stomatitis Virus (VSV) – this
pathogen’s proteins act similarly to those of rabies virus.
Researchers in Dr. Harty’s lab are most interested in the
molecular events that lead to virus assembly and budding and
focus on the viral matrix proteins (M proteins) that serve as
the building blocks of the virus particle. It’s those M proteins
that work to orchestrate the function of assembly and
budding and therefore spread of the virus within a body.
In addition to studying the relationship between how
these viral M proteins interact with host proteins to facilitate
the budding process, Dr. Harty’s lab is also interested in
understanding the host’s innate immune response to virus
infection and identifying antivirals that can inhibit the spread
of the virus.
“Host proteins are hijacked by the virus to help with
budding,” said Dr. Harty. “But if we find an inhibitor to
prevent that interaction, we could prevent the virus from
spreading. It’s called ‘host-directed therapeutics.’”
But his lab isn’t focused on rabies for rabies’ sake.
Dr. Harty and colleagues are using what they learn from
the rabies virus to apply it to other viruses that assemble and bud similarly, like Ebola and Marburg and other hemorrhagic
“Ebola and rabies viruses, they bud similarly,” said Dr.
Harty. “So if you find the inhibitor to block one, you could
block many others.”
Those others include HIV, Marburg and arenaviruses, such
as Lassa fever.
Some of these viruses are considered likely bioterrorism
agents and are on the high priority list of the Center for
Disease Control and National Institutes of Health. High
priority agents pose a risk to national security because they
can be easily disseminated or transmitted, have potential for
major public health impact and could cause widespread panic.
If Dr. Harty’s lab can understand the mechanism of virus
budding, then candidate drugs can be identified and presented
to slow down the assembly/budding process and give the
immune system an opportunity to begin fighting the pathogen.
“Vet schools are on the front line in terms of identifying
and combating pathogens,” said Dr. Harty. “Many diseases
are zoonotic in origin so if we can understand how a virus
works we can more quickly act if and when it jumps to the
Solving the MRSA Mystery
(MRSA) infections are
caused by a strain of
staph bacteria that does
not respond well to the
kinds of antibiotic drugs
normally used to treat
them. Because of that,
they can be particularly
challenging to the
human doctors trying
to treat a patient and
frustrating and painful
for the patient.
If left untreated,
infections (of the skin
and soft tissues) can
progress to cause potentially life-threatening infections in a
person’s bones, joints, bloodstream and lungs.
So, when a MRSA scare strikes, public health experts and
human physicians are called in to contain hysteria. People
are told to wash their hands well and often, keep wounds
covered, shower after working out and keep sheets on their
But in some cases, the cycle – and the infection –
continues, leaving patients and doctors confused and
And it’s when he hears about cases like these that Daniel
O. Morris, DVM, MPH, section chief of dermatology and
allergy at Ryan Hospital and professor of dermatology, brings
a different point of view to the table.
“When a person has contracted a drug-resistant staph
infection, you have to look at the entire household,” said
Dr. Morris. “You have to ask the human patient, ‘Do you
have any pets?’”
Pets are, according to Dr. Morris, a potential link in
the cycle of infections within a household. Although pets
typically carry a different species of Staph bacteria than do
people, they are still capable of becoming silent carriers of
the MRSA bacteria, just like their human counterparts. They
can also develop MRSA infections, but their role in passing
infections back to people is poorly characterized at the
It’s that potential link – of pets passing infections back to
people – that Dr. Morris, in conjunction with the Perelman
School of Medicine and Johns Hopkins, is looking at in a
recently launched study. In it, Dr. Morris and his human
medicine colleagues are specifically examining the prevalence
of MRSA bacteria on pets and their bedding in households
where a family member has a recurring MRSA infection.
The study will also assess the persistence of Staph carriage
by the pet, when the household and family members
undergo a treatment intervention. It’s an important step in
understanding the relationships between people and their pets
and the appropriateness of how close we should allow our
best friends to be.
In the case of a recurring infection, is the person living
with a pet? And is the pet sleeping in the bed? Giving kisses?
Is the pet a dog that serves in a therapy capacity and goes on
hospital visits, where the likelihood of contracting MRSA is
greater? If so, and the pet is a “silent carrier,” the recurring
infection of a household member could potentially be related
to close pet contact, and this relationship will need to be
adjusted to put an end to the cycle.
But just the simple question of “Do you own a dog?” isn’t
often in a medical doctor’s repertoire.
“Veterinarians need to be involved when a physician
suggests a pet-to-person link,” said Dr. Morris. “It’s what
they do. They’re trained to ask different questions and they
understand the human-animal bond a little better than a
medical doctor might. The pet is the member of the family
– they’re sleeping in the same bed, licking people’s faces. It’s
what’s in the journals we read and it’s what we talk about as
part of our daily practice.”
Defining Disease Biomarkers
Cutaneous leishmaniasis is an ugly disease. A protozoan
parasite transmitted by sand flies, leishmaniasis may not sound
familiar to many in the U.S., but for the people of Brazil
and across the Middle East
and Afghanistan, the disease
is much more prevalent. In
Corte de Pedra, Brazil there are
approximately 1,000 new cases
And it is there that Phillip
Scott, PhD, associate dean
for research, professor of
microbiology and immunology,
focuses his research.
There are two types of
the parasite – cutaneous and
visceral. Dr. Scott’s lab focuses on the cutaneous disease,
which causes skin lesions, hair loss and dermatitis. The
parasite affects people, as well as dogs.
“It’s similar to leprosy,” said Dr. Scott.
(The visceral type leads to swollen lymph nodes, weight
loss, decreased appetite, nose bleeds and, eventually, kidney
What is interesting about the cutaneous disease is that
some individuals have a severe reaction to infection while
others have more mild reactions.
In his laboratory, Dr. Scott and his colleagues are working
to define biomarkers to understand this discrepancy in
reaction. Based on an individual’s immune response, his lab
may be able to successfully fight infection with the help of a
drug, while others may need repeated treatments.
When early lesions are identified, an individual
goes through a 21-day treatment of receiving the drug
If however, within the first 15 days of infection, a
biomarker is identified that shows a person will not respond
to that treatment, the attending physician can jump straight
to the second treatment option, which involves a stronger,
more expensive drug.
“There’s no vaccine, treatment isn’t great,” said Dr.
Scott, “but if we can identify the biomarkers of those people
who don’t respond well with the traditional first round of
treatment, we can go straight to the second option – a better,
more expensive drug.”
In a recent paper published in The Journal of Immunology,
Dr. Scott and co-investigators point out a probable link
between the relationship of T cell response and the
likelihood of the cutaneous lesions returning. That is, the
inability of lymph nodes to recruit lymphocytes may mean a
greater likelihood of a chronic, recurring condition in certain
“Understanding how these parasites circumvent generating
a strong immune response allows us to design new therapies
to enhance immune responses in patients, and thus promote
more rapid cure of the disease,” said Dr. Scott.