''Baculoviridae'' is a family of

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...

es.

Arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...

s, among the most studied being

Lepidoptera Lepidoptera ( ) is an order of insects that includes butterflies and moths (both are called lepidopterans). About 180,000 species of the Lepidoptera are described, in 126 families and 46 superfamilies, 10 percent of the total described speci ...

Hymenoptera Hymenoptera is a large order of insects, comprising the sawflies, wasps, bees, and ants. Over 150,000 living species of Hymenoptera have been described, in addition to over 2,000 extinct ones. Many of the species are parasitic. Females typic ...

and

Diptera Flies are insects of the order Diptera, the name being derived from the Greek δι- ''di-'' "two", and πτερόν ''pteron'' "wing". Insects of this order use only a single pair of wings to fly, the hindwings having evolved into advanced ...

, serve as natural hosts. Currently, 85

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...

are placed in this family, assigned to four genera. Baculoviruses are known to infect insects, with over 600 host species having been described. Immature (larval) forms of lepidopteran species (moths and butterflies) are the most common hosts, but these viruses have also been found infecting

sawflies Sawflies are the insects of the suborder Symphyta within the order Hymenoptera, alongside ants, bees, and wasps. The common name comes from the saw-like appearance of the ovipositor, which the females use to cut into the plants where they lay ...

, and

mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...

es. Although baculoviruses are capable of entering mammalian cells in culture, they are not known to be capable of replication in

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

ian or other

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...

animal cells. Starting in the 1940s, they were used and studied widely as

biopesticide A Biopesticide is a biological substance or organism that damages, kills, or repels organisms seens as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships. They are obtained from organisms inclu ...

s in crop fields. Baculoviruses contain a circular, double-stranded DNA (dsDNA) genome ranging from 80 to 180 kbp.

Historical influence

The earliest records of baculoviruses can be found in the literature from as early as the 16th century in reports of "wilting disease" infecting

silkworm The domestic silk moth (''Bombyx mori''), is an insect from the moth family Bombycidae. It is the closest relative of '' Bombyx mandarina'', the wild silk moth. The silkworm is the larva or caterpillar of a silk moth. It is an economically ...

larvae. Starting in the 1940s, the viruses were used and studied widely as biopesticides in crop fields. Since the 1990s, they have been employed to produce complex eukaryotic

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s in insect

cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...

s (see Sf21,

High Five cells High Five (BTI-Tn-5B1-4) is an insect cell line that originated from the ovarian cells of the cabbage looper, '' Trichoplusia ni.'' It was developed by the Boyce Thompson Institute for Plant Research. High Five cells have become one of the most com ...

). These recombinant proteins have been used in research and as

vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.

s in both human and veterinary medical treatments (for example, the most widely used vaccine for prevention of

H5N1 Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type ...

avian influenza in chickens was produced in a baculovirus expression vector). More recently, baculoviruses were found to transduce mammalian cells with a suitable promoter.

Baculovirus lifecycle

The baculovirus lifecycle involves two distinct forms of virus. Occlusion-derived virus (ODV) is present in a protein matrix (polyhedrin or granulin) and is responsible for the primary infection of the host. while the budded virus (BV) is released from the infected host cells later during the

secondary infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...

. Baculoviruses have very species-specific tropisms among the

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chorda ...

s with over 700 host species having been described. Immature (larval) forms of lepidopteran species are the most common hosts, but these viruses have also been found infecting sawflies and mosquitoes. Reports of baculovirus infections of

shrimp Shrimp are crustaceans (a form of shellfish) with elongated bodies and a primarily swimming mode of locomotion – most commonly Caridea and Dendrobranchiata of the decapod order, although some crustaceans outside of this order are ref ...

and beetles (e.g. ''Oryctes rhinocerus'') were found to be nudiviruses, a closely related lineage to the baculoviruses. Typically, the initial infection occurs when a susceptible host insect feeds on plants that are contaminated with the occluded form of the virus. The protein matrix dissolves in the alkaline environment of the host midgut (stomach), releasing ODVs that then fuse to the columnar

epithelial cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

membranes A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

of the host intestine and are taken into the cell in

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

Nucleocapsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

s escape from the endosomes and are transported to nucleus. This step is possibly mediated by

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

filaments. Viral transcription and replication occur in the

cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

and new BV particles are budded out from the basolateral side to spread the infection systemically. During budding, BV acquires a loosely fitting host cell membrane with expressed and displayed viral

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...

After baculovirus infection, three distinct phases occur: * Early (0–6 h), * Late (6–24 h) * Very late phase (18–24 to 72 h) While BV is produced in the late phase, the ODV form is produced in the very late phase, acquiring the envelope from host cell nucleus and embedded in the matrix of occlusion body protein. These occlusion bodies are released when cells lyse to further spread baculovirus infection to next host. The extensive lysis of cells frequently causes the host insect to literally disintegrate, thus the reason for the historic name "wilting disease". The complete ODV-polyhedrin particles are resistant to heat and light inactivation, whereas the naked BV virion is more sensitive to environment. When infecting a caterpillar, the advanced stages of infection cause the host to feed without resting, and then to climb to the higher parts of trees, including exposed places they would normally avoid due to the risk of predators. This is an advantage for the virus if (when the host dissolves) it can drip down onto leaves, which will be consumed by new hosts.

Structure of the virion

The most studied baculovirus is ''Autographa californica multicapsid nucleopolyhedrovirus'' (AcMNPV). The virus was originally isolated from the alfalfa looper (a lepidopteran) and contains a 134 kbp

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...

with 154

open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readi ...

s. The major capsid protein VP39 together with some minor proteins forms the nucleocapsid (21 nm x 260 nm) that encloses the DNA with p6.9 protein. BV acquires its envelope from the cell membrane and requires a glycoprotein, gp64, to be able to spread systemic infection. This protein forms structures called peplomers on one end of the budded virus particle, but is not found on ODVs (although several other proteins are only associated with the ODV form). Some differences also exist in the lipid composition of the viral envelope of the two forms. While the BV envelope consists of phosphatidylserine, ODV contains phosphatidylcholine and phosphatidylethanolamine. A nucleocapsid assembly-essential element (NAE) was identified in the AcMNPV genome. The NAE is an internal ''cis''-element within the ''ac83'' gene. The nucleocapsid assembly is not dependent on the ''ac83'' protein product.

Major envelope glycoprotein gp64

During periods of evolution, the baculoviral envelope glycoproteins have undergone changes. Ld130, also known as baculovirus F-protein from ''Lymantria dispar'' (LdMNPV) is suggested to be an ancestral envelope fusion protein which has been replaced by non-orthologous gene replacement with gp64 in AcMNPV, ''Bombyx mori'' (BmNPV) and ''Orgyia pseudotsugata'' (OpMNPV) while they still retain the ld130 gene. Gp64 is a homotrimeric membrane glycoprotein that is polarly present on the rod-shaped virion. It consists of 512

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

s (aa) with four glycosylation sites at asparagine residues and has a N-terminal signal sequence (20 aa), oligomerization and fusion domain and a hydrophobic transmembrane domain near the C-terminus (7 aa). It is produced in both early and late phases of the infection cycle with a maximal rate of synthesis occurring in 24–26 h after infection. Trimerization with intermolecular cysteine-bonds seems to be a crucial step for protein transport to cell surface, since only 33% of synthesized protein reaches cell surface, as monomeric gp64 is degraded within the cells. Gp64 is essential for efficient budding of the virion and for the cell-to-cell transmission during the infection cycle, as well as viral entry, i.e. causing viral trophism and endosome-mediated uptake to the cell. The major function of the gp64 envelope protein is to cause the pH-mediated envelope fusion to the endosome. Although gp64 has variety of essential functions, it has been reported that gp64-null baculoviruses can be substituted with other viral glycoproteins such as Ld130, G-protein of ''Vesicular stomatitis'' virus. These substitutions will result in functional virons.

Applications

Baculovirus expression in insect cells represents a robust method for producing recombinant glycoproteins or membrane proteins. Baculovirus-produced proteins are currently under study as therapeutic cancer vaccines with several immunologic advantages over proteins derived from mammalian sources.

Biosafety

Baculoviruses are incapable of replicating within the cells of mammals and plants. They have a restricted range of hosts they can infect that is typically restricted to a limited number of closely related insect species. Because baculoviruses are not harmful to humans, they are considered a safe option for use in research applications. They are also used as biological agents as in the case of the Indian mealmoth, a grain-feeding pest.

Taxonomy

The name of this family has been derived from the Latin word ''baculus'', meaning "stick". The family has been divided into four genera: '' Alphabaculovirus'' (lepidopteran-specific nucleopolyhedroviruses), '' Betabaculovirus'' (lepidopteran-specific granuloviruses), '' Gammabaculovirus'' (hymenopteran-specific nucleopolyhedroviruses), and'' Deltabaculovirus'' (dipteran-specific nucleopolyhedroviruses).

Evolution

Baculoviruses are thought to have evolved from the ''

Nudiviridae This category is for articles about virus families (or redirects to such articles). There should be no subcategories. families Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (b ...

'' family of viruses .

References

External links

ICTV Report: ''Baculoviridae''

* Index of Viruses – Baculoviridae (2006). In: ICTVdB – The Universal Virus Database, version 4. Büchen-Osmond, C (Ed), Columbia University, New York, USA. https://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_index.htm * Rohrmann, G.F. 2019. Baculovirus Molecular Biology 4th Ed. https://www.ncbi.nlm.nih.gov/books/NBK543458/ * Rohrmann, G.F. 2019. Baculovirus Molecular Biology 4th Ed. https://ir.library.oregonstate.edu/concern/defaults/7d279043k?locale=en {{Authority control Biopesticides Diptera pests and diseases Insect viral diseases Virus families Mind-altering parasites