Question

Walk me through the steps of poxvirus entry, replication, and spread.

Answer 1

Poxviruses are brick or oval-shaped viruses with large double-stranded DNA genomes. Poxviruses exist throughout the world and cause disease in humans and many other types of animals. Poxvirus infections typically result in the formation of lesions, skin nodules, or disseminated rash.

Entry:

There is fusion of viral membrane with plasma membrane to get entry into host cell.pox virus have  two infectious forms of virus, the single-membrane MV and the double-membrane EV. On theoretical grounds alone it seemed unlikely that the outer EV membrane would fuse since that would leave a membrane bound MV-like particle in the cytoplasm. Single MV membrane Fuse with the plasma membrane of the cell .Engulfment of the large particles by the celloccurs by clathrin- and caveolin-independent macropinocytosis or fluid phase endocytosis and is dependent on actin dynamics and cell signaling.The requirement for cell signaling may have led to earlier proposals that chemokine receptors serve as poxvirus entry portals EVs may enter through the plasma membrane or following endocytosis.MVs can enter cells via neutral pH plasma membrane or low pH endocytic pathways. There are Four viral proteins can mediate MV attachment which are  D8 binds chondroitin sulfate and A27 and H3 proteins bind heparan sulfate indicating the importance of glycosaminoglycans .

REPLICATION

poxviruses depends upon heavily on virus-encoded proteins which enable them to replicate in the cytoplasm. the virus membrane- is bound particle contains a core, within which reside the linear, double-stranded DNA genome and virus-encoded enzymes and factors that allow transcription of the early set of genes. When the core enters the cytoplasm, early mRNA and protein synthesis occur, followed by DNA replication. The replicated DNA provides a template for the synthesis of intermediate and late classes of mRNA. Following late gene expression, virus assembly begins. The initial infectious form, called a mature virions (MV), has a single external membrane. Some MVs are wrapped in a modified trans-Golgi or endosomal membrane to become triple-membrane particles called wrapped virions (WVs), whereas other MVs remain free or in inclusions within the cytoplasm until liberated by cell lysis. The WVs are transported on microtubules to the periphery of the cell where the outer membrane fuses with the plasma membrane to release an extracellular enveloped virion (EV), consisting essentially of a MV with one additional membrane. At least 20 proteins are associated with the MV membrane and 6 others with the outer (enveloped virion) EV membrane. Mature virus (MVs) are very stable and are thought to mediate transmission between host animals, whereas EVs have a fragile outer membrane and are specialized for exiting the intact cell and spreading within the host. EVs can remain associated with the tips of actin-containing protrusions at the cell surface or released into the surrounding fluid . Mutations of other EV proteins can also increase EV release. A high percentage of EVs that are released from cells have a partly disrupted outer membrane.

spreading

The virus produces a protein, vaccinia growth factor (VGF), that mimics epidermal growth factor, a protein that stimulates the growth of healthy cells and plays a key role in activating cell movement thus spreading through out the host body.

Poxviruses are transmitted between individuals by several routes: by aerosol and droplets (variola virus), by introduction of virus into small skin abrasions after direct or indirect contact with an infected animal (orf virus, milker’s nodule virus), and in the case of some animal poxviruses mechanically by biting arthropods. The viruses generally have narrow host ranges. Poxviruses are resistant to degradation in the environment at ambient temperatures and may survive many years in dried scabs or other virus-laden material.

All poxvirus infections are associated with lesions of the skin, which may be either localized or widespread. The lesions associated with many diseases are pustular, but lesions due to molluscum contagiosum virus, parapoxviruses, and yatapoxvirus are proliferative. Generalized poxvirus infections have a stage of leukocyte-associated viremia, which leads to localization of virus in the skin and to a varying extent in internal organs. Immunity to such infections is prolonged. However in some localized poxvirus infections, notably those produced by parapoxviruses, immunity is short-lived and reinfection is common.

Most human poxvirus infections occur through minor abrasions in the skin. Orf, molluscum contagiosum and monkeypox viruses cause the most frequent poxvirus infections worldwide. Individuals with atopic dermatitis may be predisposed to poxvirus infections such as molluscum contagiosum, orf or cowpox.