- A research team
carried out a study to identify how HIV overcomes the great barriers of
the mucosal bottle neck to invade the body of the host.
- Certain strains
of the HIV 1 virus were 3 times more infectious and 1.4 times increased
ability to replicate.
- They were more
resistant to IFN-alpha2 and IFN-beta of the immune system than other
AIDS virus has to overcome huge barriers, during an intercourse, to identify
the target cell and to result in a new infection. The virus has to move past
the genital mucosa and make its way through the epithelial cells that are
tightly packed together and meant to keep invading infections away. Another considerable step in the path of the
AIDS virus is to move past the immune system,
which includes the type 1 interferons. Not every unprotected contact results in the development of a HIV infection
in fact only 1 in 1000 unprotected exposures has been found to result in a successful HIV-1 infection.
Beatrice Hahn, professor of Medicine and Microbiology at the University of
Pennsylvania wanted to identify what was unique about the transmission of these
viruses that aided in their ability to infect. According to Dr. Hahn, the human body has many barriers that prevent the entry of viruses.
‘Certain HIV strains have developed advanced mechanisms of entry into the host.’
Dr. Hahn and her research team studied the nature of these HIV-1 strains to
determine how they successfully passed through the genital mucosa, which formed the boundary of entry for various
viral isolates from the genital secretions and blood of 8 donors with chronic
HIV infection and their matched recipients were studied. The researchers
identified a sub population of HIV- 1
strains which had biological properties that enabled them to efficiently cause
new infections. The results of the
findings were published in a study in Proceedings
of the National Academy of Sciences
Findings of the Study
- 300 virus
isolates were identified by the research team from individual HIV-1
particles that were found to infect the donors as well as the matched
- Recipient viruses
were three times more infectious than viruses isolated form the donors.
- The recipient
viruses had a 1.4 increased ability to replicate.
- They were significantly more resistant to the anti-viral effects of
interferons, IFN-alpha2 and IFN-beta.
- The transmitted
viruses when compared to donor viruses needed an 8-fold higher
concentration of IFN-alpha2 along with
a 39-fold higher concentration of IFN-beta in order to be able to produce
a 50% reduction in replication.
- The odds of the
strains of HIV that were found to be interferon-resistant, where the
highest IFN-alpha2 and IFN-beta doses were 35-fold and 250-fold greater.
Iyer, who is the doctoral student and the first author of the study stated that
this means that the rapidly multiplying strains of interferon resistant HIV
strains had higher transmission fitness. According to the author, this was
confirmed pretreating CD4 immune cells with interferon before the virus was
isolated. The donor isolates were thus selected based on whether they had a
virus like phenotype.
recipient isolates were found to be released from the infected CD4 cells more
efficiently than the donor isolates. The important aspect of the transmission
is the production of cell free particles.
study was able to identify the factors of the virus that was able to overcome
the mucosal bottleneck. The HIV-1 strains that were able to replicate and which
were able to spread efficiently even when they were faced with a strong immune
reaction were the ones that were successful in moving past the mucosal
the properties of the virus that was able to confer the ability to transmit the
virus even though there were considerable barriers in the human body could be
used in the development of treatment for HIV-1
infection. Dr. Hahn stated that they still do not know which of the viral gene
products provided the resistance to interferon, but understanding these
mechanisms will aid in providing new targets for AIDS prevention
as well as therapy.
Primary HIV-1 Infection
HIV-1 infection can occur through mucosal
barriers or through inoculation. The dendritic cells are the first to attack
the viruses when the HIV-1 binds to the
receptors of the dendritic cells. At
this stage, it was believed that the
dendritic cells were antigen presenting cells that aided in priming T cells
with raid infection of the T cells.
are two separate sites of binding of the HIV 1 virus
- The CD4+ T cell
- A 7-transdomain
entry of the HIV-1 virus in to the cell then leads to the integration of the
virus into the genetic material of the host. HIV-1 dissemination soon occurs to
the CNS with rapid viral replication in actively infected cells. The time taken
for viremia is 4-11 days, though the development of symptoms may take many
initial infection of HIV-1 requires a highly
dynamic relationship between virus and host. The symptoms that develop are
associated with a large amount of virus in the body and the response of the
host's immunological process.
identification of the exact mechanism that exists for the entry of certain
strains of HIV into the body can be used to strengthen the immune system as
well as develop new strategies for treatment. This would not only prevent the
spread of infection but will also provide new targets for therapy.
- Shilpa S. Iyer, Frederic Bibollet-Ruche, Scott Sherrill-Mix, Gerald H. Learn, Lindsey Plenderleith, Andrew G. Smith, Hannah J. Barbian, Ronnie M. Russell, Marcos V. P. Gondim, Catherine Y. Bahari, Christiana M. Shaw, Yingying Li, Timothy Decker, Barton F. Haynes, George M. Shaw, Paul M. Sharp, Persephone Borrow, Beatrice H. Hahn. Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness. Proceedings of the National Academy of Sciences, 2017; 201620144 DOI: 10.1073/pnas.1620144114
- Primary HIV Type 1 Infection - (http://cid.oxfordjournals.org/content/38/10/1447.full)