Discovery presents new challenges for HIV eradication efforts
The most critical barrier for curing HIV-1 infection is the presence of the viral reservoir, the cells in which the HIV virus can lie dormant for many years and avoid elimination by antiretroviral drugs. Very little has been known about when and where the viral reservoir is established during acute HIV-1 infection, or the extent to which it is susceptible to early antiretroviral therapy (ART).
Now a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) in collaboration with the U.S. Military HIV Research Program has demonstrated that the viral reservoir is established strikingly early after intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before detectable viremia.
The findings appear online in the journal Nature.
"Our data show that in this animal model, the viral reservoir was seeded substantially earlier after infection than was previously recognized," explains senior author Dan H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC and steering committee member of the Ragon Institute of MGH, MIT and Harvard. "We found that the reservoir was established in tissues during the first few days of infection, before the virus was even detected in the blood."
This discovery coincides with the recently reported news of the HIV resurgence in the "Mississippi baby," who was believed to have been cured by early administration of ART. "The unfortunate news of the virus rebounding in this child further emphasizes the need to understand the early and refractory viral reservoir that is established very quickly following HIV infection in humans," adds Barouch, a Professor of Medicine at Harvard Medical School.
In this new study, the scientific team initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIV infection. Animals treated on day 3 following infection showed no evidence of virus in the blood and did not generate any SIV-specific immune responses. Nevertheless, after six months of suppressive ART, all of the animals in the study exhibited viral resurgence when treatment was stopped.
While early initiation of ART did result in a delay in the time to viral rebound (the time it takes for virus replication to be observed in the blood following cessation of ART) as compared with later treatment, the inability to eradicate the viral reservoir with very early initiation of ART suggests that additional strategies will be needed to cure HIV infection.
"The strikingly early seeding of the viral reservoir within the first few days of infection is sobering and presents new challenges to HIV-1 eradication efforts," the authors write. "Taken together, our data suggest that extremely early initiation of ART, extended ART duration, and probably additional interventions that activate the viral reservoir will be required for HIV-1 eradication."
Study coauthors include first author James Whitney of BIDMC and the Ragon Institute of MGH, MIT and Harvard; BIDMC investigators Srisowmya Sanisetty, Pablo Penaloz-MacMaster, Jinyan Liu, Mayuri Shetty, Lily Parenteau, Crystal Cabral, Jennifers Shields, Stephen Blackmore, Jeffrey Y. Smith, Amanda L. Brinkman, Lauren E. Peter, Sheeba I. Mathew, Kaitlin M. Smith, Erica N. Borducchi; Aliso L. Hill and Daniel I. S. Rosenbloom of Harvard University; Mark G. Lewis of Bioqual, Rockville, MD; Jillian Hattersley, Bei Li, Joseph Hesselgesser, Romas Geleziunas of Gileas Sciences, Foster City, CA; and Merlin L. Robb, Jerome H. Kim and Nelson L. Michael of the Walter Reed Army Institute of Research.
This study was supported, in part, by the US Military Research and Material Command and the US Military HIV Research Program through its cooperative agreement with the Henry M. Jackson Foundation (W81XWH-07-2-0067; W81XWH-11-2-0174); the National Institutes of Health (AI060354; AI078526; AI084794; AI095985; AI096040; AI100645) and the Ragon Institute of MGH, MIT and Harvard.
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently ranks third in National Institutes of Health funding among independent hospitals nationwide.
BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Health Care, Beth Israel Deaconess HealthCare, Community Care Alliance, and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Senior Life and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.
Bonnie Prescott | Eurek Alert!
The herbivore dilemma: How corn plants fights off simultaneous attacks
09.02.2016 | Boyce Thompson Institute for Plant Research
Shedding Light on Bacteria
09.02.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
Indications of light-induced lossless electricity transmission in fullerenes contribute to the search for superconducting materials for practical applications.
Superconductors have long been confined to niche applications, due to the fact that the highest temperature at which even the best of these materials becomes...
Researchers at King’s College London and the Wellcome Trust Sanger Institute in the United Kingdom have for the first time demonstrated a direct link between the Wbp2 gene and progressive hearing loss. The scientists report that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mouse as well as in two clinical cases of children with deafness with no other obvious features. The results are published in EMBO Molecular Medicine.
The scientists have shown that hearing impairment is linked to hormonal signalling rather than to hair cell degeneration. Wbp2 is known as a transcriptional...
Pollens, the bane of allergy sufferers, could represent a boon for battery makers: Recent research has suggested their potential use as anodes in lithium-ion batteries.
"Our findings have demonstrated that renewable pollens could produce carbon architectures for anode applications in energy storage devices," said Vilas Pol, an...
Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...
09.02.2016 | Event News
02.02.2016 | Event News
26.01.2016 | Event News
09.02.2016 | Event News
09.02.2016 | Materials Sciences
09.02.2016 | Power and Electrical Engineering