Viral Harpoon Structure Suggests Measles, HIV And Ebola Viruses Related

March 26, 1999



March 26, 1999
–When viruses infect cells, they employ molecular "harpoons" to snare their intended target. Recently, a team of scientists identified and determined the three-dimensional structure of the harpoon protein used by a large family of pathogenic viruses to grab hold of and fuse to host cells. Surprisingly, the protein's structure suggests that viruses that cause measles and mumps may be viral cousins of HIV, influenza and Ebola virus.

The research team, which included Robert Lamb of the Howard Hughes Medical Institute at Northwestern University, believes that its discovery may help lead to the development of drugs that can prevent viral infections by jamming this critical infectious machinery. The researchers reported their findings in the March 26, 1999, issue of the journal Molecular Cell.

Lamb and Northwestern University colleagues Theodore Jardetzky, Kent Baker and Rebecca Dutch were studying a member of the paramyxovirus family, which includes the viruses that cause measles, mumps and respiratory syncytial viral infection (RSV) – a leading cause of hospitalization in young children. Other paramyxoviruses cause croup, pneumonia and bronchitis in young children, and members of this family can infect a variety of mammals and birds. The scientists crystallized the fusion protein of a paramyxovirus that infects monkeys and used x-ray crystallography to determine the protein’s three-dimensional structure. This analytical process involves shining an intense x-ray beam through a protein crystal, and then deducing the protein’s structure by analyzing the patterns of light that emerge from the crystal.

Although the scientists studied the fusion protein of only one paramyxovirus, they are confident that the structural finding applies to the entire paramyxovirus family. Previous analyses of the basic "primary" structure – the order, or sequence, of amino acids that make up a protein – of many different paramyxovirus fusion protein molecules revealed that their basic structures are all similar.

But when the scientists analyzed the three-dimensional structure of the simian virus fusion protein, they were surprised to discover close structural similarities to fusion proteins from HIV, influenza and Ebola, said Lamb. Aside from this similarity, he said, "all these viruses have very different strategies for infecting cells and insinuating viral genetic material into the target cells to commandeer their machinery."

According to Lamb, the similarity among such widely varied viruses suggests that they might have had some common ancestor that shared a primitive version of the fusion protein. It is impossible at this point, however, to pinpoint the evolutionary origin of that ancestry, he said.

Regardless, said Lamb. "knowing the structure of this one fusion protein may lead to the development of drugs capable of thwarting the action of the fusion proteins of other members of the paramyxovirus family, and even possibly its distant viral cousins." At the least, he added, these findings will spur further studies involving other medically important viruses.

Specifically, determining the three-dimensional structure of the fusion protein sheds new light on the key event in paramyxovirus infection — when the virus unfolds itself to reveal a spikelike protein that is launched into the gel-like outer membrane of the target cell. "It's much like a harpoon going into a target," said Lamb.

He emphasized, however, that more research is needed to answer two important questions: What triggers the harpoon molecule to unfurl, and how does the fusion protein refold itself to draw the virus toward the ensnared target cell? "What happens there is a mystery," he said. "It's like spearing a shark. It’s relatively easy to spear it, but getting it onboard the boat is more difficult, and we don’t quite know how this kind of process happens in these viruses."
-end-


Howard Hughes Medical Institute

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.