A bioactive phlebovirus-like envelope protein in a hookworm endogenous virus
Monique Merchant1,2, Carlos P Mata1,2, Yangci Liu1,2
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Science Advances
|May 11, 2022
Summary
New genes can emerge from endogenous viral elements (EVEs). Researchers discovered an intact retrovirus-like EVE in hookworms, revealing a novel viral fusion protein structure and activity.
Area of Science:
- Virology
- Genomics
- Structural Biology
Background:
- Endogenous viral elements (EVEs) comprise 15% of the human genome and represent a source of novel genetic material.
- Nematode EVEs are exceptionally diverse and offer insights into viral evolution.
Purpose of the Study:
- To identify and characterize novel endogenous viral elements (EVEs) in the human hookworm *Ancylostoma ceylanicum*.
- To elucidate the structure and function of the Atlas virus envelope protein, particularly its fusion capabilities.
Main Methods:
- Identification of an intact retrovirus-like EVE, termed Atlas virus, in *Ancylostoma ceylanicum*.
- Cryo-electron microscopy (cryo-EM) to determine the structure of the Atlas GC protein.
- Functional assays to assess the membrane fusion activity of Atlas GC.
Main Results:
- Discovery of the Atlas virus EVE, encoding a GC envelope protein related to Phenuiviridae.
- The cryo-EM structure of Atlas GC reveals a class II viral membrane fusion protein fold, previously unobserved in retroviruses.
- Atlas GC exhibits characteristics of an active fusogen, inserting into endosomal membranes at low pH and mediating cell-cell fusion.
Conclusions:
- The Atlas GC protein possesses structural and functional similarities to active viral fusogens, despite its retroviral origin.
- This finding highlights the structural plasticity of reverse-transcribing RNA viruses and suggests EVEs can retain biological activity.
- The Atlas GC protein may evolve to acquire new cellular functions.
Related Concept Videos
01:28Introduction to Virus
277
Viruses are unique biological entities that blur the boundary between living and non-living systems. Although they lack cellular structure and metabolic processes, they can exhibit characteristics of life when infecting a host. Their defining feature is a nucleic acid core, composed of either DNA or RNA, encapsulated within a protein coat called a capsid. This simple structure allows them to invade host cells and use their machinery for replication efficiently.Viral Structure and...
277
02:28Leaky Scanning
5.3K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.3K
01:38Intralumenal Vesicles and Multivesicular Bodies
3.8K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.8K
02:33Retroviruses
12.7K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.7K
01:29Subviral Agents
144
Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
144
00:56Viral Structure
64.7K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
64.7K