Virology term - assembly, exit and entry. Flashcards Preview

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Key points in viral structure essay.

Function of a virion
Restrictions on structure


Functions of a virion (4)

To package all genetic material + necessary proteins
To protect genetic material
To bind correct cell.
To deliver genetic material to correct compartment.


Delivery of genome and structure

Must be metastable structure: energy barrier prevents degradation, but can be overcome.


Limitations on structure

Limited coding capacity - use symmetry, either helical or platonic polyhedra.


How do you describe helical structures?

P = μ x ρ
where μ = number of structural units per turn,
where ρ = rise per structural unit,
where P = pitch of helix.


Helical nucleocapsid structures

Tobacco mosaic (just genome and capsid protein), paramyxo, rhabdo, orthomyxo.


Icosahedral structure

20 triangular faces, 12 vertices related by 2,3 and 5 fold symmetry. 60 identical subunits.



Caspar and Klug.
T = triangulation number = number of structural units per face.
Non-covalent binding in different positions is similar but not identical. Pentamers maintained, but extra hexamers added.


Symmetry in helical capsids

Rotation and translation.


Example of small icosahedral virus.

Canine parvovirus.


Example of large icosahedral virus.

Tomato bushy stunt virus. T=3. Monomers have jelly-roll barrel formation.
Human rhinovirus.


Pseudo T=3

More than one structural protein, which are structurally similar but not identical.


Hiding binding sites

1) In canyon too narrow for antibodies e.g. ICAM-1 binding site in human rhinovirus. Pocket factor stabilises until binding.
2) Using glycosylation


Structure in treatment

Druggable binding pocket (rhinovirus).
Stabilising empty capsid with covalent bonds (FMDV).


Rhabdovirus nucleocapsid.

No specific interaction between N and RNA bases. 9 RNA molecules bind groove between N protein domains.


Rhabdovirus matrix protein

M protein required for condensation into tight helix. Forms another helix round N protien. Polymerisation links M layers to each other.


HSV capsid

VP5 is major protein for pentons and hexons. VP26 lies on top.
VP23 and VP19C form triplexes between hexons/pentons.


Unique herpesvirus structure

Portal formed by VP6


Dengue virus proteins

Capsid, membrane, envelope and 7 non-structural.


Dengue E protein.

With long prM protein on surface which needs pr peptide removed by furin in maturation.
Low pH induces large movement of domain two, switches from dimer to trimer.


Maturation of HIV-1

Cleavage of Gag by viral protease (dimer) --> conformational change. MA remains with lipid membrane. NC and RNA condenses. CA reorganises to form capsid. Forms fullerene core


Different structures of vaccinia virus

Immature virion - no envelope.
Intracellular mature virion - single envelope.
Intracellular enveloped virion - triple envelope.
Cell-associated enveloped virion - double envelope.
Extracellular enveloped virion, double envelope.


Basic virus assembly plan

Encapsidation of genome, selection of genome, localisation of virion components, acquisition of tegument, acquisition of envelope, escape from the cell, maturation events.


Encapsidation of genome mechanism.

Concerted assembly (either), empty shell (icosahedral). Requirement of chaperones or not.


Mechanism for selection of genome.

Specific signal, non-specific packaging, segmented viruses.


Localisation of viral components in assembly.

Virus factories, host export pathways, nuclear localisation.


Ways to acquire a membrane

At host membrane, in vesicular pathways.


Escaping the cell - details.

Downregulation of receptor, deal with tetherin.


Capsid assembly not requiring scaffold proteins.

Poliovirus. Will self-assemble into capsids in cell-free translation system.


Capsid assembly requiring scaffold proteins.

Adenovirus needs them at 2 stages.
Herpesviridae family - removal of scaffolds requires protease and pH drop with DNA entry.
Polyomavirus VP1 can form aberrant capsid but needs hsp70 to form proper one.


Example of empty shell assembly.

Herpesviridae, entry via portal.
Adenovirus, mechanism not fully understood.


Concerted assembly.

Nucleation via binding of proteins to genome e.g. helical structures, HIV.
Can drive transcription-assembly transition if packaging region overlaps with promoters.


Virion assembly: selection of genome, SV40.

SV40 uses ses (italics) signal on genome. Cellular protein Sp1 recognises this, binds VP2/3, shuts down transcription and acts as nucleation point.


Virion assembly: selection of genome, herpes viridae.

Terminase subunit binds pac1/2 and docks at portal.
pUL15 has ATPase activity and pumps it into the capsid.
UL15 then cleaves DNA.


Model for genome segment selection in segmented dsRNA viruses.

Daisy chain or core filling models.
Not fully understood, but panhandle structures may be important.


Reoviridae - concerted assembly model.

RNA associated polymerase complexes associate. The core shell assembles round this.


Reoviridae - core filling model.

Polymerase complexes assemble with proteins to give complete shell. RNAs are inserted individually, concomitant synthesis of complementary strand.


Virion assembly - Localisation of proteins and genome.

In viral factory. Using host export machinery. Nuclear localisation machinery.


Virion assembly - nuclear localisation machinery - influenza virus and adenovirus

Influenza uses this. M1 imported in to asssociate with RNPs, then core genomic complex is exporeted.
Adenovirus: hexon trimerisation depends on L4-100K and cytosolic chaperones. Import depends on NLS on protein VI.


Virion assembly - localisation using host trafficking.

Common. E.g. HIV-1 uses this. Env synthesised in ER, trafficked to Golgi, cleaved by furin, trafficked via secretory pathway to plasma membrane. Interacts with Gag or is endocytosed.
MARV: nucleocapsid uses PT/SAP late domain to recruit Tsg101 for trafficking to membrane. ESCRT machinery.


Process of budding.

Accumulation of proteins at budding site.
Membrane deformation.
Membrane scission.


Accumulation of proteins at budding site, HIV.

Formation of budding site necessary because more cellular than viral proteins. Use protein interactions or lipid rafts. HIV depends on cholesterol and sphingolipid rich domains. Requires PIP2 as unsaturated fatty acid is displasced into Gag.


Membrane deformation.

Preformed capsids associating with membrane proteins.
Association of proteins causing membrane curvature - Gag, M1 polymerisation, VP40 rearrangement.
Possibly uses lipid rafts.


Membrane scission without ESCRT

Alphaviruses: precise stoichiometry. Semliki Forest virus.


ESCRT machinery.

ESCRT I binds membrane, recruits ESCRT II.
Bro1 and ESCRT I/II recruit ESCRT III, ubiquitination involved.
ESCRT III causes constriction of neck and scission.


Hijacking ESCRT I.

Recruited by HIV-1 tsg101 by p6 domain of Gag via PT/SAP, MARV VP40 via PPPY


ESCRT III action.

ESCRT III form tapering spirals or whorls that pull opposing membranes towards central fission spot. 3 models. Vps4A/B is an ATPase which drives scission. Spiralling CHMP4 subunits important. Vps4 may help form these by recycling CHMPs, or drive hemi-fission to completion.


Hijacking ESCRT III.

HIV recruits using ALIX. L domains of viruses often hijack this.


Exporting a virion from the nucleus - hepadnaviridae

Hepadnavirus; small enough to exit through the pores.


Herpesviridae exit from nucleus.

Bud into INM. In HSV this uses gD and gH, but doesn't in pseudorabies.
Nuclear envelopment complex includes pUL31 and pUL34 disrupts the nuclear lamina and associates with the membrane.


Nucleation site helical -ive ssRNA viruses.

Encapsidation occurs during synthesis (sometimes). Rdrp can act as nucleation point.


Nuclear localisation for assembly - polyomavirus

Polyomaviruses use this. VP1 most likely to import if with VP2/3, so probably import as pentamer. Localisation within nucleus to PML bodies depends on VP2/3 signals. Localisation of genome depends on Large T antigen.


Virion assembly selection of genome: adenovirus.

ψ, packaging signal, contains copies of A repeat.
Viral proteins IVa2 and L4-22K bind this.
IVa2 probably drives entry.


Accumulation of proteins at budding site, HCMV

Or target to specific budding compartment. E.g. HCMV formation of virion assembly compartment.


Segmented genome selection, influenza A.

5' and 3' ends important. Intersegment base-pairing creates packaged complex of 8 segments. Daisy-chain model = they each interact with one on each side. Master segment model = they all interact with central segment.


Herpesvirus full egress model.

Buds into INM, de-envelopment by unknown mechanism. Acquires tegument. Buds into golgi-derived vesicles and then is trafficked out by secretory pathways.


Herpesvirus proteins in budding



Poxvirus assembly

Single lipid bilayer around virus core forms immature virion. Forms on scaffold made of D13.
IMV form s after proteolytic cleavage and core condensation.
Wrapping of IMV particles adds 2 lipid bilayers to form IEV.


Non-enveloped virus exit

Lysis, autophagy, exosome pathway.


Topics to consider in viral entry essay

Enveloped vs non-enveloped.
Mechanisms of entry (druggable?).
Receptor specificity.
Effects on host cell.


Similarities in entry between enveloped and non-enveloped.

Both are metastable entities. Both can be taken up by endocytosis.


Receptor binding env vs non-env.

Enveloped: spike proteins.
Non-enveloped: projections or indentations of the capsid.


Endocytosis of viruses

May require movement to an endocytic hotspot.
Often protects from host immune defences.
Can make conformational change pH dependent.


Mechanisms of viral endocytosis

Clathrin coated pit
Caveolar pathway
Clathrin and dynamin independent pathway.
Fluid phase uptake.


Clathrin-dependent endocytosis.

Usually used for receptor internalisation; invaginations form that pinch off using dynamin.
Matures into early endosome, sheds protein pit, acidifies.
Late endosomes continue to acidify.
Viral fusion occurs at either EE or LE, may require proteolysis.


Caveolar dependent endocytosis.

Dynamin and cholestrol dependent, slow, takes virus to pH neutral caveosomes.


Clathrin and dynamin independent internalisation pathways.

Involves endocytosis of GPI-anchored proteins with fluid to give GEECs, which are very acidic.


Fluid phase uptake

Stimulated by growth factor receptors.
Primarily actin driven, can be acidified, vaccinia taken up like this.


Poliovirus uptake

Clathrin and caveolin independent uptake. Requires tyrosine kinase dependent pathway.


Attachment factors

Concentrate virus on cell surface, do not cause change in viral anti-receptor.


Rare alternative to attachment factor.

HPV. Wounding allows access to basment membrane. Leads to conformational change and L2 cleavage, which exposes L2 epitope, which allows transfer of virions to epithelial cell surface.


Define receptor

An attachment factor or protein whose binding is necessary to trigger uptake or conformational change.


Viruses requiring only one receptor

Influenza HA and sialic acid.
VSV G and phophatidylserine.


Co-receptors example.

HIV gp120 - CD4 and CCR5 or CXCR4.
Coreceptor tropism may change between strains or over time.


HIV R5 and transmission

Traditionally thought to be macrophage trophic. Recent suggestion is that there are a series of inefficient barriers that are better overcome by R5 rather than 1 efficient one.
R5s are only ones commonly causing transmission.


Non-enveloped entry

Tightly coupled with conformational change.
Pore formation.
Membrane disruption.


Non-enveloped pore formation

Only nucleic acid enters. E.g. poliovirus.


Poliovirus delivery of genome

Forms homo-multimeric size-selective membrane pore.
Pvr binds 160S. This expels pocket factor and causes conformational change.
VP1 N-terminus and myristoyl of VP4 externalise and form a pore. VP3 plug domain shifts and the RNA exits. Druggable target.


Non-enveloped membrane disruption example.

Adenovirus. pH change leads to flipping of N-terminal domain of amphiphathic helix out of protein VI, inserts into membrane causing its lysis.


Stages of membrane fusion

stalk, hemifusion and pore intermediates


Alternative to producing membrane bound free viral particles.

cell to cell spread.


Membrane fusion receptors: class 1

trimer of trimers


Membrane fusion receptors class 1. Viral families.

Similar to proteins used in vesicular fusion. Retroviruses, influenza viruses, paramyxoviruses, filoviruses.


Membrane fusion receptors class 1. Mechanism.

Fusion peptide liberated by proteolytic processing or pH change.
Trigger leads to formation of extended intermediate, which is embedded in both membranes. Collapse of the intermediate leads to hemifusion, and drives this to completion.


Fusion peptides.

• Usually type 1 glycoproteins with short hydrophobic stretch – the fusion peptide.
• N-terminal fusion peptides
• Internal fusion peptides


N-terminal fusion peptides

orthomyxo,paramyxo, some retro


Internal fusion peptides.

Rous sarcoma virus, VSV, Ebola, MHV.


Further steps to influenza entry after membrane fusion

M2 channel allows acidification of interior, possibly leads to M1 conformational change. Result: RNPs released into cytosol.


Membrane fusion receptors Class 2. Families

Flaviviruses, alphaviruses. Based on B-sheets not a-helices.
Classic example: Dengue.


Membrane fusion receptors class 2.

Trimers from dimers.


Membrane fusion receptors - Dengue.

E protein fusigenic, prM protein cleaved to give M.
PrM/E form trimers. Processing of prM leads to E forming homodimers. pH change leadst to E homotrimers concomitant with insertion of fusion loop.


Membrane fusion receptors - class 3.

Non-spring loaded class; reversible as no proteolytic processing.


Membrane fusion receptors - class 3: families.

Rhabdoviruses, herpesviruses.


Membrane fusion receptors - class 3. Triggers.

Rhabdo: pH,
Herpes: conformational change in partner protein.


Membrane fusion receptors - class 3. Mechanism.

 Example: VSV G fusion mechanism
Pre-fusion trimer with fusion loop held near viral membrane.
Hypothetical extended conformation leads to postfusion conformation.


Herpes virus entry proteins.

gB/C for attachment.
gD has conformational change
gB and gHgL interact with the cellular membrane to cause fusion.


Things to consider in receptor specificity.

Disease tropism.
Constraints on evolution.
Manipulation in vector delivery.
Druggable targets.


HA and 2,3 vs 2,6-sialic acid.

Birds and horses have 2,3-sialic acid (linear) at sites of virus entry, humans 2,6 (more folded). Acts as one of the species barriers. Requires two substitutions and loss of glycosylation site to effectively overcome, although a single substitution improves 2,6-sialic acid binding. Alter binding, but also alter stability.


Receptor specificity, disease tropism: examples

HA and sialic acid.
Receptor based resistance - CCR5


Receptor based resistance - CCR5

CCR5 deletion homozygotes protective against acquisition of HIV, delays death in heterozygotes.


Entry: beyond the plasma membrane. Topics.

Effects of binding.
Delivery of effector proteins.
Delivery to the correct compartment.


Effects of binding

Altered uptake
Modulation of signalling cascades.
Delivery of PAMPs.


Effects of binding: altered uptake.

CD4+ binding triggers signaling turning on actin co-regulator cofilin, disrupting cortical actin, aiding viral entry.


Effects of binding: signalling. Examples

Coxsackie virus B
HIV gp120
Binding integrins.


Effects of binding: signalling. Coxsackie virus B.

Binding leads to DAF clustering.
Abl activation, Rac activation, actin reorganization and movement to the tight junction and binding of CAR, necessary for particle conversion
Fyn activation, caveolin phosphorylation and virus entry at the tight junction.


Effects of binding: signalling. HIV gp120.

Binding CD4 leads to either activation or anergy.
Chemokine receptors leads to cytoskeletal rearrangements, alterations in host transcription and chemotaxis.


Binding of integrins

Stimulates endocytosis, conformational change and other.


Effects of binding: signalling. HCMV.

Binds growth factor receptor, stimulates host cell metabolic activity.


Effects of binding: pathogenesis. Example

 Influenza and some other respiratory viruses bind epithelial amiloride-sensitive sodium channel resulting in fluid accumulation, coughing and sneezing. Helps transmission, causes symptoms.


Delivery of proteins altering cellular milieu - example

Lateral bodies in vaccinia – VH1 is a phosphatase which dephosphorylates STAT1 to prevent interferon-y-mediated viral responses.


Delivery to the correct compartment.

Use endocytosis.
Exposure of sequences due to capsid destabilisation.
Nuclear entry.


Nuclear entry mechanisms

Enter during mitosis (some retroviruses)
Small: through via nuclear pore (HBV)
Long and thin: through nuclear pore (flu)
Uncoating at nuclear membrane and delivery of genome through pore. Ejection of DNA due to conformation change. Viruses with portals: this may be significant here.


Ways to identify receptors.

Viral anti-receptor as affinity hook.
Functional cloning
Inhibitory antibody based assay.


Identifying HIV co-receptors

 Use HeLa cells. In some express viral gp120, in others express HeLa cDNA library.
 Fusion of cell detected
 cDNA library subfractionation used to home in on co-receptors


Caveats to lab work in identifying receptors.

 Viral concentrations might be different
 Virus may become tissue-culture adapted
 Cultured cells may be different from cells in natural tissues.


HIV co-receptors

mannose binding protein, DC-SIGN. Possibly tether to allow interactions with suboptimal levels of CD4+?


HIV uncoating

Occur somewhere between PM and nuclear pore.
MA phosphorylation by MAP kinase may have a role of some sort.
Cyclophilin A is a cellular factor packaged in virions which may have a role.


DNA flap

Involved in nuclear entry of PIC.


Pre-integration complex

dsDNA, IN, MA, Vpr, RT


Pox virus entry

Uncoating in 2 stages. First outer membrane removed during entry into cell, then the next membrane is uncoated in the cytoplasm.


Virus budding essay

Virus budding basics
ESCRT mechanism
Recruitment of ESCRT
Other techniques


Intro to virus budding essay

Compare with fusion: most encode own fusion proteins, but use host budding proteins.
Virus budding sheds light on ESCRT mechanisms.


Places viruses bud

Plasma membrane - HIV, influenza.
Acquired in ER or Golgi: flavi, herpes.
Acquire in cytoplasmic viroplasm: pox.


Energy for membrane deformation.

Protein-protein interactions.


Why use ESCRT?

Only known machinery to perform membrane scission with reverse topology to endocytosis.


ESCRT model system

Genetic analysis in yeast.
Used for formation of multivesicular bodies, among others.


Late domains used to recruit ESCRTs

At least 5 different classes - discovery of new classes often leads to discovery of new ESCRT proteins.
Retrovirus gags e.g HIV p6 : PTAP
Rhabdovirus M protein : PSAP, PPxY
Filovirus : VP40 : PTAP, YPXL, PPXY


PTAP recruits



YPxL recruits

Alix, a Bro-1 protein


PPxY recruits

Nedd4-like ubiquitin ligases.


Models for ESCRT III.

ESCRT-III filaments could form tapering spirals or whorls that pull the opposing membranes toward a central fission point
the “dome”, “whorl”, and "hourglass" models
and/or spiraling filaments constrict membranes by sliding past themselves, assistance of VPS4 (e.g., the “break and slide” and “purse string” models).


Ubiquitin dependent recruitment of ESCRT III>

Retroviral virions concentrate ubiquitin and ubiquitin depletion inhibits virus budding.
Covalent ubiquitin can sometimes function as a late assembly domain when fused directly to retroviral Gag proteins.
The known early-acting mammalian ESCRT factors ALIX, ESCRT-I and ESCRT-II, all contain ubiquitin-binding domains (UBDs);
genetic analyses indicate that ALIX binding to K63-linked ubiquitin chains enhances EIAV and HIV-1 budding


Some new potential late domains.




New potential late domain. “FPIV” within the M proteins of the paramyxoviruses human Parainfluenzavirus Type 5 (hPIV-5) and Mumps



New potential late domain. AMOTL1 can also bind hPIV-5 M and facilitate virus release


NEDD4 family members.

New potential late domains?
in several cases, NEDD4 family members can stimulate release of retroviral Gag proteins that lack PPXY late assembly domains, implying novel interaction modes
HIV-1 overexpression of NEDD4L can “rescue” the release and infectivity of viral constructs that lack TSG101 and ALIX binding sites



The actin remodeling protein IQGAP is required for efficient release of Ebola virus-like particles. IQGAP also can bind the structural proteins of Ebola and MLV and can bind TSG101


HIV budding - example for ESCRT.

Driven by gag
Recruited to membrane by myristate
Final step requires ESCRT
Otherwise you get particle on a stalk


Herpesvirus egress and budding - ESCRT

ESCRTIII but not I and II and essential for herpesvirus egress
siRNA showed hsv1 budding with Alix, ESCRT1 and 2 knockdown
Vps4 negative mutants no budding
Multiple redundant pathways for viral recruitment
But ESCRT machinery essential for scission
Not required for nuclear egress which is driven by the interaction between pUL31 and pUL34


Alphavirus budding

Precise stoichiometry provides energy for membrane scission.
Semiliki forest viruse : COCKBURN 2004
E1/E2 trimers of spike protein
E2 tail interacts with capsid protein
Precise interaction of 80 spike: 240 capsid drives membrane scission.


Paramyxovirus budding

RSV - Require a functional Rab11 pathway
Unclear whether this is due to budding
Rab11 typically intracellular vesicle trafficking
Sendai virus uses requires actin.


Orthomyxovirus budding

Use viral proteins.
Vps28 and Vps4 independent
M1 polymerisation and M2 scission
M2 ampipathic helix sufficient for membrane fission in vitro
Antiviral target?
Filamentous forms


Pox virus acquiring membrane

Denovo lipid membrane synthesis
Triple layered particle


Non-enveloped viruses using ESCRT

Blue tongue: Reovirus
Picornavirus : Hep A
Hep C within exosomes


Herpes egress overview

Capsid and DNA encapsidation.
Perinuclear virions.
Fusion with ONM.
Acquisition of tegument proteins.
Budding into trans-Golgi network.


Herpes egress - nuclear exit.

Unlikely to be through pores, since too large, and pores intact til late in infetion.
Fusion of perinuclear particle clearly seen: budding into INM then fusion with ONM widely accepted.
Breakdown of nuclear envelope rare.


Herpes egress. Fusion with ONM.

Mechanism unknown.


Herpes egress - proteins in nuclear exit

Some evidence for a role of entry (fusion) proteins gB or gH in HSV-1 nuclear egress
Good evidence for NO role of gB, gD, gH or gL in pseudorabies virus (swine alphaherpesvirus) nuclear egress
Viral kinase US3 is important for efficiency of perinuclear particle fusion (deletion viruses have increased numbers of perinuclear virions)
Possible cellular proteins involved


Tegumentation of herpesvirus.

Two routes: Recruitment to free capsids
Recruitment to the cytoplasmic domains of viral envelope proteins
Tegument can be divided into two layers, an inner tegument layer (capsid bound) and an outer tegument layer (envelope associated)


Capsid - inner tegument interaction.

The ‘most’ inner tegument protein is thought to be VP1/2 (UL36) a very large protein of >3000 aa that can interact with UL37, UL25 and VP16.


Herpesvirus portal - tegument around it.

Extra tegument density specifically around portal complex has been resolved by cryo-EM
Currently unknown what protein(s) contribute to this density
Could be VP1/2 in a different or more stable structure
This would fit with a likely role of VP1/2 during genome release at nuclear pores after entry
Could be terminase subunit(s) that remain attached after genome encapsidation (unlikely)
Or any other tegument protein


Single-Molecule Localisation Microscopy: dSTORM

Very precise localised imaging technique using reconstruction.


Localisation of tegumentation.

1) VP1/2 contains an NLS and can directly interact with the capsid/CCSC protein UL25 and so could be acquired in the nucleus
2) Some reports have shown the presence of VP1/2 on capsids within the nucleus but not likely since no evidence of this if nuclear egress is inhibited.
3) Others reports showing VP1/2 is only present in the cytoplasm
4) Some tegument proteins have been observed in perinuclear virions (US3 and VP16) – evidence that some tegument can be acquired before nuclear egress.
5) The vast majority of the tegument proteins are certainly acquired in the cytoplasm


Membrane protein localisation

During their synthesis, membrane proteins are co-translationally inserted into the ER membrane.
Secretory pathway to get to plasma membrane.
Endocytic pathway to prevent sustained expression.


Herpesvirus secretory pathway from ER.

After correct folding, glycosylation, disulphide bond formation etc., the default pathway for membrane proteins is to exit the ER in transport vesicles and travel sequentially through the Golgi stack, the trans-Golgi network (TGN) and then reach the plasma membrane


Herpesvirus endocytic pathway to ER.

Upon reaching the cell surface, some membrane proteins can be internalised via endocytosis and targeted to a variety of endocytic organelles: early endosomes, sorting endosomes, late endosomes, lysosomes or the TGN


Herpes glycoprotein M

When expressed on their own, both gD and gH/L localise to the plasma membrane.
When these glycoproteins are co-expressed with gM, they localise to intracellular membranes.
gM one mechanism by which herpesviruses can localise membrane proteins to the correct compartment for final envelopment.
gM also drags them back to endosomes, from the surface.


HSV envelope protein localisation mechanisms.

Other HSV-1 proteins also involved in localising gD and gH/L
Glycoprotein K (+UL20) also required for gH/L internalisation
Redundancy between gM and gK/UL20 for gD internalisation


Transport of enveloped herpes virion to surface.

Transport of virion containing vesicles is achieved using microtubles and kinesins (+ end directed motors)
Little understanding of mechanism – viral membrane proteins gE and US9 may bind kinesin
Cellular pathways (SNAREs, Rabs, tethers) most likely involved