Dear Asraf,

Based on my Knowledge, HCV cannot infect platelets. Platelets are mature cells without nucleus and the transcription activity is limited in these cells. As a result the intracellular condition of platelets are not optimum for replication of HCV. I think thrombocytopenia in some cases of HCV infection can be as result of bone marrow suppression caused by the virus. However, you should remember that megakaryocytes in the bone marrow have the potential to get infected by the virus which can result in thromobcytopenia.

Yours,

Heidar

Thanks

At the moment there are no studies on this issue. However it is important to point out that platelet progenitor cells have all the cellular machinery to allow HCV replication.

I do not know if this could be useful to you but the molecular mimicry of hepatitis C virus protein with platelet GPIIIa is responsible for immunologic thrombocytopenia.

we studied platelets and have shown that they do carry HCV. Indeed, it is a very likely mechanism of viral spread. We also initiated a microvescicle study.

To my knowledge there is no evidence to suggest that HCV replicates in platelets. However, HCV replication is entirely cytoplasmic and thus the virus is potentially able to replicate in platelets. I must add that minus strand HCV RNA can be found in several cells, predominantly mononuclear cells although this is not sufficient evidence in favour of true HCV replication in a given cell.

Dear Prof. Agree. Comprehensive answer.

I agree with Heidar Sharafi that HCV cannot infect platelets. For thrombocytopenia seen in Patients with HCV, antibodies against HCV must be remembered.

please do study literature on cell entry by HCV, cell to cell transmission, mechanisms of replication, and perform experiments demonstrating that our study on platelets carrying AND replicating for at least one cicle HCV and producing envelope proteins within platelets can be considered not true. Until then it is true that at least one replication cicle was demonstrated, and new envelope proteins transcribed and synthetized.

Antonio has apparently solid evidence of (limited?) HCV replication in platelets as supported by detection of transcripts and viral proteins. Antonio did you use culture-derived HCV such as the JFH-1 strain isolated and propagated by Wakita to infect platelets? That would strengthen your evidence.

I agree with Dr Sharafi. The main causes for thrombocytopenia in HCV infections are hypersplenism and autoimmune phenomenon.

HCV has been reported for some time in extrahepatic sites such as peripheral blood mononuclear cells and platelets.

During chronic HCV infection, thrombocytopenia is a haematological disorder that is often detected. There may be a direct viral effect since a positive correlation between thrombocytopenia and HCV association with platelets has been found (de Almeida et al., 2004)

However, a variety of different mechanisms are thought to contribute to thrombocytopenia and to be related to hypersplenism (Nagamine et al., 1996; Pockros et al., 2002; Sanjo et al., 2003) including the sequestration of platelets in the enlarged spleen (Sanjo et al., 2003). Impaired hepatic production of thrombopoietin has been proposed (Ishikawa et al., 1998; Martin et al., 1997; Peck-Radosavljevic et al., 1997). The medication of platelet destruction mediated by immunoglobulin such as platelet-associated IgG that may possibly leading to the sequestration in the reticuloendothelial system has been suggested.

Platelets do not express CD81 on their cell surface and so alternative mechanisms for infection must be considered. HCV from plasma or purified from infected patients interacts specifically with the extracellular Ig-like domains of human platelet GPVI and the interaction appears not to be mediated by E2. HCV interaction with GPVI might explain, at least partially, the viral binding to platelets in infected patients (Astrid Zhan 2006) (Márcia Paschoal do Espírito-Santo). Platelet load of viraemia is associated with response to treatment and acting as a reservoir of infedtion.

I hope this is helpful and all the references are in Pubmed.

There have been studies that report platelets contain HCV and possibly HCV replicating in them. I think it is a topic that needs further investigation. There have been numerous studies that show HCV replicating in a variety of cell types, so it is plausible that HCV replicates in platelets. I don't think experiments using JFH-1 are very useful, as they it is not a typical HCV strain.

Thanks dr Annwyne_Houldsworth for the nice review on cause of thrombocytopaenia with chronic HCV infection. Indeed it is a common findiing in HCV patients from Egypt

Autoantibodies against platelets are present in the circulation of a proportion of cirrhotic patients carrying HCV. Among cirrhosis patients- in our experience- 90% were also carriers of pathogenic strains of H.pylori, a well known inducer of autoAb against platelets. Byrne et al (Gastroenterology ) showed that 2 of 5 H pylori strains studied bind vW factor and GPIIa on platelets. A Lancet letter by Gasbarrini A.et al indicated that cure of H pylori reported platelets count to normal within six months in 33% of "autoimmune" thrombocytopenic patients. Acute autoimmune thrombotic thrombocytopenic purpura was shown clearly linked to H.pylori infection, also in some HCV-positive cirrhotics.

A medical phenomenon can originate from more than one single pathogenic mechanism. Multiple concomitant causes may well exist in a common disease.

In Southern Italy HCV was shown present in the circulation of of 34 to 50% of people aged 60 and over (e.g Stroffolini et al Hepatology). At the same age, 50% to 70%( or more ) of the population carry Hpylori, hence coinfection could be frequent. As far as I know there is no test able to detect which strain in which patient could induce autoimmunity against platelets.

I have a provocative supplemental question: once demonstrated that HCV may infect and replicate in platelets what is the consequence? If platelets act as extra hepatic site of replication what's the clinical impact apart of supposed decrement in platelets count? Do someone may provide information on significative increased platelets count, once HCV was cleared in cirrhotic patients?

Results on HCV replication in PBMC tried to explain HCV-associated mixed crioglobulinemia, and possibly lymphoma, while provided contrasting data on its effect on the response to standard anti-HCV therapy. So, platelets infection by this virus could result in the activation of coagulation cascade, and increased risk of stroke, or Increased risk of plasmocytoma?

It seems from the current evidence that HCV induced thrombocytopenia is related to many factors other that direct infection of the blood platelets. The most frequently encountered cause is the enhanced destruction by hyperactive spleen, sequestration in the enlarged spleen, defective thrombogenesis due liver diseases with reduced thrombopiotien, increases platelet destruction due to immune related mechanism. In my opinion, direct infection of platelets by HCV, if occurred, plays minor role in thromocytopenia.