Virusreaktivierung EBV, CMV, VZV (ELISpot): the pathway in the body

Virusreaktivierung EBV, CMV, VZV (ELISpot) is part of the pathway “Herpesviruses: latency and reactivation”. This page shows the whole pathway; the station of Virusreaktivierung EBV, CMV, VZV (ELISpot) is highlighted.

Where this laboratory value sits: Spot in the ELISpot — one responding cell. In the ELISpot, blood cells are stimulated with viral proteins. Each T cell that releases interferon-γ leaves a spot on the bottom of the plate, which is counted. Source 7

In brief

EBV, CMV and VZV are herpesviruses that remain dormant in particular cells for life after primary infection. If they become active again, virus-specific T cells recognise their proteins, remove infected cells and release interferon-γ.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Primary infection → EBV Epstein-Barr virus enters the throat via saliva and infects B cells. Its genome persists for life in resting memory B cells. Source 2↕ both, depending on amount In resting memory B cells EBV makes almost no proteins and so stays invisible to T cells; when the cell divides, the viral genome is copied along with it. established physiology Source 2
   ⚖ When the balance tips

   too much — If many B cells carry the virus, there are more starting points for reactivation, and the T cells have more to monitor.

   too little — If few B cells carry the virus, the number of dormant viruses stays small and stable.

   established physiology · Source 2, 5

2. Primary infection → CMV Cytomegalovirus lies dormant in precursor cells in the bone marrow and in monocytes. Only when these mature into tissue macrophages can it become active again. Source 3↕ both, depending on amount In the precursor cells most viral genes are silent; maturation of the host cell switches them back on, so reactivation is linked to the cell's development. established physiology Source 3
   ⚖ When the balance tips

   too much — If many infected monocytes mature into macrophages, for example during inflammation, more opportunities for reactivation arise.

   too little — If the cells stay immature, the virus stays silent.

   established physiology · Source 3

3. Primary infection → VZV After primary infection, varicella zoster virus travels along the nerves into the ganglia beside the spinal cord and cranial nerves and lies dormant in nerve cells there. Source 4↕ both, depending on amount In the nerve cells VZV makes hardly any proteins; T cells that recognise the virus help maintain this dormant state. established physiology Source 4, 6
   ⚖ When the balance tips

   too much — If VZV becomes active in a ganglion, it travels along the nerve to the skin of the corresponding skin segment.

   too little — If VZV-specific T cells remain numerous, the virus stays silent in the ganglia.

   established physiology · Source 4, 6

4. EBV → Reactivation If control by T cells weakens or the host cell is activated, the viruses switch their replication genes back on. Source 1↓ depletes On reactivation the virus again makes proteins and new viruses; the cell is usually destroyed, and viruses reach saliva, blood or skin. established physiology Source 1
   ⚖ When the balance tips

   too much — If reactivation happens often, virus-specific T cells are stimulated again and again and multiply.

   too little — If reactivation remains rare, most of the T cells rest as memory cells.

   established physiology · Source 1, 5

5. CMV → Reactivation If control by T cells weakens or the host cell is activated, the viruses switch their replication genes back on. Source 1↓ depletes On reactivation the virus again makes proteins and new viruses; the cell is usually destroyed, and viruses reach saliva, blood or skin. established physiology Source 1
   ⚖ When the balance tips

   too much — If reactivation happens often, virus-specific T cells are stimulated again and again and multiply.

   too little — If reactivation remains rare, most of the T cells rest as memory cells.

   established physiology · Source 1, 5

6. VZV → Reactivation If control by T cells weakens or the host cell is activated, the viruses switch their replication genes back on. Source 1↓ depletes On reactivation the virus again makes proteins and new viruses; the cell is usually destroyed, and viruses reach saliva, blood or skin. established physiology Source 1
   ⚖ When the balance tips

   too much — If reactivation happens often, virus-specific T cells are stimulated again and again and multiply.

   too little — If reactivation remains rare, most of the T cells rest as memory cells.

   established physiology · Source 1, 5

7. Reactivation → Viral proteins · MHC molecules The cell breaks viral proteins into fragments and displays them on MHC molecules at its surface. This makes it recognisable to T cells. Source 5↑ supplies The displayed fragments are the signal by which T cells recognise an infected cell; herpesviruses carry genes that slow this display. established physiology Source 5
   ⚖ When the balance tips

   too much — If a cell displays many viral fragments, more T cells recognise it, and faster.

   too little — If it displays few, for example because viral genes slow the display, the infected cell stays unrecognised for longer.

   established physiology · Source 5

8. Virus-specific T cell → Interferon-γ Activated T cells release interferon-γ. It puts surrounding cells on defensive alert. Source 5, 7↕ both, depending on amount Interferon-γ inhibits viral replication in neighbouring cells and increases the display of fragments on MHC molecules; in large amounts it drives inflammation. established physiology Source 5
   ⚖ When the balance tips

   too much — If a lot of interferon-γ is released, more phagocytes are activated and inflammation in the tissue increases.

   too little — If little is released, neighbouring cells display fewer fragments and viral replication is checked less strongly.

   established physiology · Source 5

9. Virus-specific T cell → Cell is removed · perforin, granzyme Cytotoxic T cells deliver perforin and granzymes to the infected cell. The cell dies before new viruses are released. Source 5↓ depletes Removing infected cells deprives the virus of its sites of replication and so ends a reactivation. established physiology Source 5
   ⚖ When the balance tips

   too much — If many infected cells are removed, the reactivation ends quickly.

   too little — If few are removed, the virus multiplies for longer and spreads further.

   established physiology · Source 5

10. Interferon-γ → Spot in the ELISpot · capture antibody In the ELISpot, blood cells are stimulated with viral proteins. Each T cell that releases interferon-γ leaves a spot on the bottom of the plate, which is counted. Source 7↑ supplies The number of spots shows how many cells in the sample respond to the respective virus. established physiology Source 7
    ⚖ When the balance tips

    too much — Many spots show many responding T cells; whether they come from an ongoing reactivation or from the memory of earlier contacts cannot be told from the test alone.

    too little — Few spots show few responding cells; this may be due to no contact with the virus or to damped T cells.

    contested · Source 7, 5

Further stations

• Primary infection — each virus separately EBV, CMV and VZV are herpesviruses. At first infection they multiply until the immune system contains them; afterwards they are never completely removed. Source 1↓ depletes In the first phase the viruses make new viruses in infected cells and destroy many of these cells; at the same time virus-specific T and B cells build up. established physiology Source 1
  ⚖ When the balance tips

  too much — If a virus multiplies strongly, it reaches more cells, and more cells carry it in dormant form afterwards.

  too little — If multiplication is checked early, the number of cells that carry the virus permanently stays small.

  established physiology · Source 1

• Virus-specific T cell — recognises the fragment T cells with a matching receptor recognise the viral fragment on the cell. They become active and release messengers. Source 5, 6↓ depletes Activated T cells remove infected cells and keep the dormant viruses in check; for EBV and CMV, a considerable share of memory T cells forms this guard. established physiology Source 5
  ⚖ When the balance tips

  too much — If many T cells are stimulated, they multiply and fill a large part of the T-cell pool with virus-specific cells.

  too little — If few virus-specific T cells are present or they work in a damped way, reactivations are contained more slowly.

  established physiology · Source 5

Cofactors in this pathway

• MHC molecules — Display viral fragments on the cell surface so that T cells can recognise them Source 5
• Perforin and granzymes — Tools of the cytotoxic T cell with which it removes infected cells Source 5
• Interferon-γ — Messenger of the activated T cell that the ELISpot makes visible as a spot Source 7
• Viral proteins (antigens) — Stimulate, in the test, the T cells that recognise exactly this virus Source 7

Sources

1. Cohen JI. Herpesvirus latency. J Clin Invest 2020 · PubMed 32364538
2. Thorley-Lawson DA. EBV Persistence--Introducing the Virus. Curr Top Microbiol Immunol 2015 · PubMed 26424647
3. Sinclair J, Sissons P. Latency and reactivation of human cytomegalovirus. J Gen Virol 2006 · PubMed 16760381
4. Gershon AA, Breuer J, Cohen JI et al. Varicella zoster virus infection. Nat Rev Dis Primers 2015 · PubMed 27188665
5. Taylor GS, Long HM, Brooks JM et al. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol 2015 · PubMed 25706097
6. Laing KJ, Ouwendijk WJD, Koelle DM, Verjans GMGM. Immunobiology of Varicella-Zoster Virus Infection. J Infect Dis 2018 · PubMed 30247598
7. Slota M, Lim JB, Dang Y, Disis ML. ELISpot for measuring human immune responses to vaccines. Expert Rev Vaccines 2011 · PubMed 21434798

Whole pathway: Herpesviruses: latency and reactivation

Related pathways

• Neopterin — interferon-γ

As of 2026-10-05. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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