• This topic covers dsDNA viruses belonging to the families Adenoviridae, Baculoviridae, Herpesviridae and nucleocytoplasmic large DNA viruses (NCLDVs).
  • The NCLDVs include large and giant viruses characterized by their large virions and genomes, and can be classified into several distinct families: Ascoviridae, Asfarviridae, Iridoviridae, Mimiviridae, Marseilleviridae, Phycodnaviridae and Poxviridae.
  • They also include members of the proposed families Pandoraviridae and Pithoviridae as well as the recently isolated molivirus and faustovirus.
  • They replicate completely or partially in the cytoplasm and are larger than other viruses.
  • Although these viruses have several common features (e.g., topology, replication and protein sequence similarities) they utilize different entry pathways to infect a wide range of hosts, including humans, other mammals, invertebrates, fish, and protozoa and algae.
  • It has been proposed that the NCLDVs be classified into one order, named “Megavirales”, whereas, herpesviruses belong to the order Herpesvirales.
  • Generally, mimiviruses and phycodnaviruses are closely related to pandoraviruses and moliviruses, whereas pithoviruses are related to marseilleviruses, iridoviruses and ascoviruses, and faustovirus are closely related to asfarviruses.


  • Adenoviruses (Ad) are non-enveloped icosahedral viruses with diameters of 70-90 nm that can be divided into seven groups and 50+ serotypes. They harbour 30 to 40-kb linear dsDNA genomes encoding around 45 proteins, and they replicate in the nucleus.

Herpesviridae (order Herpesvirales)

  • Herpesviruses (HVs) have an enveloped icosahedral virion (150-200 nm) containing a 120 to 240-kb linear dsDNA genome encoding 100-200 proteins.
  • They replicate in the nucleus.
  • The >70 known members of this family include eight human pathogens: HSV-1, HSV-2, CMV, EBV, KSHV, VZV, HHV-6 and HHV-7.
  • HVs are rich in glycoproteins (GPs) that can form heterodimeric complexes to facilitate attachment and entry.


  • Baculoviruses are an arthropod-specific enveloped viruses with nucleocapsid dimensions of 21 × 260 nm.
  • They have circular dsDNA genomes of 80-180 kb that encode 100-180 proteins and replicate in the nucleus.
  • They are used in biocontrol against insects, and as vectors for gene transfer and protein expression.
  • Consequently, their entry into an insect, human, and cancer cells has an increasing biological impact


  • Poxviruses are widely distributed enveloped viruses (∼360 × 270 × 250 nm) that replicate in the cytoplasm.
  • They harbour a 130 to 375-kb linear genome that encodes ~200 proteins.
  • Vaccinia virus (VV) is a prototypic virus of this class that was used as a smallpox vaccine.
  • It exists in three forms.
  • The first is the mature virion (MVs, also known as the intracellular mature virus, IMV or INV), which has a brick-shaped structure; it is the most abundant, stable and simple form and is active in host-host transmission.
  • The second form is the wrapped virion (WV or intracellular enveloped virus, IEV), which contains an MV core wrapped in two membranes. WVs travel to the cell periphery via microtubules and fuse with the plasma membrane, and they are then released by exocytosis as the third form, the extracellular virion (EV, or cell-associated extracellular enveloped virus, CEV, or extracellular enveloped virus, EEV), which is specialized for exiting and cell-to-cell transmission within the host.

Giant viruses (Mimiviridae and Marseilleviridae)

  • These families comprise the largest known viruses, so-called giant viruses (GVs).
  • They have genomes of ~0.5-2.5 Mb that encode 400-2500 proteins, and they replicate in the cytoplasm.
  • Representatives of these families have been isolated from diverse habitats, including bronchoalveolar lavage fluid and stools from patients with pneumonia, insects, and leeches (for a detailed review, see reference).
  • The nature of the relationship between giant viruses and pneumonia remains to be elucidated.
  • Mimivirus virions are 500 nm in diameter, with a 1 Mb dsDNA genome encoding 900 proteins. Their surfaces are completely covered with fibers (120 nm long) attached to the capsid via a disc-shaped feature except at one capsid vertex. The outer fibers may play some role in the virus’ attachment to or entry into host cells, but the details of its mechanisms of attachment and entry are unknown. Mimiviruses enter amoebae or macrophages via a phagocytosis-like mechanism that depends on dynamin, actin and PI3-K.


  • The Phycodnaviridae are marine enveloped viruses with dimensions of 100-220 nm that have 330 to 560-kb linear dsDNA genomes and replicate in the cytoplasm of algae. Despite having algal hosts, their entry pathways resemble those used by bacteriophages and animal viruses.
  • Paramecium bursaria chlorella virus (PBCV-1) attaches to host cells via a viral vertex and degrades the host cell wall at the site of attachment like a bacteriophage.
  • Emiliania huxleyi virus 86, enters host cells via endocytosis or fusion of the outer lipid membrane surrounding the capsid, which is similar to animal virus entry. The intact virion can be seen in the cytoplasm before the capsid breaks down to release the genome.
  • Ectocarpus fasciculatus virus infects zoospores or gametes of brown algae that lack cell walls. It fuses with the outer plasma membrane of the host cell, leaving the capsid outside the cell surface, and injects its genomic cargo into the cytoplasm.


  • These are enveloped viruses (175-215 nm) with 170 to 190-kb linear dsDNA genomes encoding around 150 genes.
  • They infect macrophages and monocytes of pigs and argasid ticks, and they replicate in the nucleus and/or cytoplasm.
  • The early steps in the binding and entry of the African swine fever virus (ASFV) into host cells are largely unknown.
  • The ASFV-E70 and Ba71V strains enter Vero cells and macrophages by low-pH-, dynamin-, and clathrin-dependent endocytosis, which requires actin, small GTPase Rab7 and PI3-K.
  • Additionally, cholesterol may be needed to liberate the virus from endosomes into the cytoplasm. There is also evidence that ASFV can enter via macropinocytosis, which requires actin, kinases and Na+/H+ exchange.


  • The iridoviruses include both enveloped and non-enveloped viruses with dimensions of 120-350 nm that replicate in the cytoplasm of insect and fish cells.
  • They harbour 100 to 200-kb linear dsDNA genomes with circularly permuted and redundant termini.
  • The enveloped viruses fuse with the cell membrane of the host cell, whereas the non-enveloped viruses enter via endocytic pathways.
  • Frog virus 3, tiger frog virus, and infectious spleen and kidney necrosis virus enter BHK-21, HepG2 and Mandarin fish fry cells, respectively, by endocytosis.
  • The VP088 protein encoded by SGIV facilitates both endocytosis and macropinocytosis into a grouper spleen cell line.


  • These viruses (~130 nm diameter, 200-400 nm in length) infect invertebrates; they replicate in the nucleus and harbour 150 to 190-kb circular dsDNA genomes that encode 180 proteins.
  • They are phylogenetically related to iridoviruses, and their entry mechanisms are obscure.
  • However, Heliothis virescens ascovirus-3e infections are known to require actin rearrangement.


The different virion topologies of the 12 dsDNA large and giant virus families