Perspective concerning MHC molecules in viral persistence


  • Tirasak Pasharawipas Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
  • Khurawan Kumkrong Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand
  • Rungnapa Veeramano Faculty of Medical Technology, Rangsit University, Patumthani 12000, Thailand


major histocompatibility complex, MHC molecule, pMHC, viral carrier, viral clearance, viral persistence


The persistently viral infected individuals are a major source of viral carriers.  The cause of the viral persistency has not been well understood.  The key puzzle is that some of the virally infected people can recover without any specific treatment while others persisted with the viral agent.  The effective immune cells to eliminate the viral agents are cytotoxic T cell (Tc), natural killer cell (NK), and macrophage.  Known as the adaptive immune cell, Tc plays the most crucial role in the immune clearance of the viral agent.  To be able to play its active role, Tc requires induction of pMHC which is a complex molecule of MHC (major histocompatibility complex) and a viral epitope.  Each specific pMHC activates the compatible Tc clone through its receptor (Tc cell receptor).  MHC gene alleles are highly polymorphic.  The individual MHC variant possesses a different groove that is capable to bind a different range of antigenic epitopes.  Without the compatible MHC molecule, in general, Tc clones cannot be activated by a particular viral epitope.  This could be a reason to explain why some of the virally infected individuals cannot clear the viral agent out of their body perfectively and become the source of the viral carriers.  This article discusses the association of the MHC molecule and the cause of viral persistency in some individuals.


Abendroth, A., Kinchington, P. R., & Slobedman, B. (2010). Varicella zoster virus immune evasion strategies. Current topics in microbiology and immunology, 342, 155-171. DOI: 82_2010_41

Bello-Morales, R., & López-Guerrero, J. A. (2018). Extracellular vesicles in Herpes viral spread and immune evasion. Frontiers in microbiology, 9, 2572. DOI:

Bhaskaran, M., Murali, S. V., Rajaram, B., Krishnasamy, S., Devasena, C. S., Pathak, A., ... & ArunKumar, G. (2019). Association of HLA-A,-B, DRB, and DQB Alleles with Persistent HPV-16 Infection in Women from Tamil Nadu, India. Viral immunology, 32(10), 430-441. DOI:

Boot, H. J., Hahné, S., Cremer, J., Wong, A., Boland, G., & van Loon, A. M. (2010). Persistent and transient hepatitis B virus (HBV) infections in children born to HBV-infected mothers despite active and passive vaccination. Journal of viral hepatitis, 17(12), 872-878. DOI: 10.1111/j.1365-2893.2009. 01247.x

Carpenter, D., Hsiang, C., Jiang, X., Osorio, N., BenMohamed, L., Jones, C., & Wechsler, S. L. (2015). The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) protects cells against cold-shock-induced apoptosis by maintaining phosphorylation of protein kinase B (AKT). Journal of neurovirology, 21(5), 568-575. DOI:

Chan, L., Asriel, B., Eaton, E. F., & Wyatt, C. M. (2018). Potential kidney toxicity from the antiviral drug tenofovir: new indications, new formulations, and a new prodrug. Current opinion in nephrology and hypertension, 27(2), 102-112. DOI: 10.1097/MNH.0000000000000392

Chen, Y., Zhao, Y., Hammond, J., Hsu, H. T., Evans, J., & Feldlaufer, M. (2004). Multiple virus infections in the honey bee and genome divergence of honey bee viruses. Journal of invertebrate pathology, 87(2-3), 84-93. DOI:

de Almeida, B. S., Silva, G. M., da Silva, P. M., Perez, R., Figueiredo, F. A., & Porto, L. C. (2011). Ethnicity and route of HCV infection can influence the associations of HLA with viral clearance in an ethnically heterogeneous population. Journal of viral hepatitis, 18(10), 692-699. DOI:

Doi, T., Kwon, H. J., Honda, T., Sato, H., Yoneda, M., & Kai, C. (2016). Measles virus induces persistent infection by autoregulation of viral replication. Scientific reports, 6, 37163. DOI: 10.1038/srep37163

Drozina, G., Kohoutek, J., Jabrane-Ferrat, N., & Peterlin, B. M. (2005). Expression of MHC II genes. Current topics in microbiology and immunology, 290, 147-170. DOI:

Duffy, S. (2018). Why are RNA virus mutation rates so damn high? PLoS biology, 16(8), e3000003. DOI:

Fan, S., Wang, Y., Wang, S., Wang, X., Wu, Y., Li, Z., ... & Xia, C. (2018). Polymorphism and peptide-binding specificities of porcine major histocompatibility complex (MHC) class I molecules. Molecular immunology, 93, 236-245.DOI:

Fares-Gusmao, R., Rocha, B. C., Sippert, E., Lanteri, M. C., Áñez, G., & Rios, M. (2019). Differential Pattern of Soluble Immune Markers in Asymptomatic Dengue, West Nile and Zika Virus Infections. Scientific reports, 9(1), 17172. DOI:

Feng, J. Y. (2018). Addressing the selectivity and toxicity of antiviral nucleosides. Antiviral chemistry & chemotherapy, 26, 2040206618758524. DOI:

Flegel, T. W. (2001). The shrimp response to viral pathogens. Proceedings of the special session on sustainable shrimp aquaculture, World Aquaculture (190-214). Orlando, Boca Raton, USA: World Aquaculture Society.

Flegel, T. W. (2020). Research progress on viral accommodation 2009 to 2019. Developmental and comparative immunology, 112, 103771. DOI:

Furuya-Kanamori, L., Cox, M., Milinovich, G. J., Magalhaes, R. J., Mackay, I. M., & Yakob, L. (2016). Heterogeneous and dynamic prevalence of asymptomatic influenza virus infections. Emerging infectious diseases, 22(6), 1052-1056. DOI:

Fuller, M. J., Shoukry, N. H., Gushima, T., Bowen, D. G., Callendret, B., Campbell, K. J., ... & Walker, C. M. (2010). Selection‐driven immune escape is not a significant factor in the failure of CD4 T cell responses in persistent hepatitis C virus infection. Hepatology, 51(2), 378-387.DOI:

Gokhale, N. S., Vazquez, C., & Horner, S. M. (2014). Hepatitis C Virus. Strategies to Evade Antiviral Responses. Future virology, 9(12), 1061-1075. DOI:

Heeney, J. L. (2015). Ebola: Hidden reservoirs. Nature, 527(7579), 453-455. DOI: 527453a

Hewitt E. W. (2003). The MHC class I antigen presentation pathway: strategies for viral immune evasion. Immunology, 110(2), 163-169. DOI:

Hoarau, J. J., Bandjee, M. C. J., Trotot, P. K., Das, T., Li-Pat-Yuen, G., Dassa, B., ... & Gasque, P. (2010). Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. The Journal of Immunology, 184(10), 5914-5927. DOI: 10.4049/ jimmunol. 0900255

Hume, D. A. (2008). Macrophages as APC and the dendritic cell myth. Journal of immunology (Baltimore, Md.: 1950), 181(9), 5829-5835. DOI:

Ignuzzi, M., López, C. B. (2019). Defective viral genomes are key drivers of the virus–host interaction. Nature Microbiology, 4, 1075-1087. DOI:

Jin, Z., Kinkade, A., Behera, I., Chaudhuri, S., Tucker, K., Dyatkina, N., ... & Deval, J. (2017). Structure-activity relationship analysis of mitochondrial toxicity caused by antiviral ribonucleoside analogs. Antiviral research, 143, 151-161. DOI:

Jaggi, U., Matundan, H. H., Tormanen, K., Wang, S., Yu, J., Mott, K. R., & Ghiasi, H. (2020). Expression of murine CD80 by herpes simplex virus 1 in place of latency-associated transcript (LAT) can compensate for latency reactivation and anti-apoptotic functions of LAT. Journal of virology, 94(6), e01798-19. DOI:

Kang, H., Wang, Y., Tong, Z., & Liu, X. (2020). Retest positive for SARS-CoV-2 RNA of "recovered" patients with COVID-19: Persistence, sampling issues, or re-infection? Journal of medical virology, 92(11), 2263-2265. DOI:

Kanno, T., Ishihara, R., Hatama, S., & Uchida, I. (2018). A long-term animal experiment indicating persistent infection of bovine coronavirus in cattle. The Journal of veterinary medical science, 80(7), 1134-1137. DOI:

Kelly, A., & Trowsdale, J. (2019). Genetics of antigen processing and presentation. Immunogenetics, 71(3), 161-170. DOI:

Kłysik, K., Pietraszek, A., Karewicz, A., & Nowakowska, M. (2020). Acyclovir in the treatment of herpes viruses - A review. Current medicinal chemistry

Kondo, Y., Ueno, Y., & Shimosegawa, T. (2011). Dysfunction of immune systems and host genetic factors in hepatitis C virus infection with persistent normal ALT. Hepatitis research and treatment, 2011, 713216. DOI:

Lapa, D., Garbuglia, A. R., Capobianchi, M. R., & Del Porto, P. (2019). Hepatitis C Virus Genetic Variability, Human Immune Response, and Genome Polymorphisms: Which Is the Interplay? Cells, 8(4), 305. DOI:

Lázaro, S., Gamarra, D., & Del Val, M. (2015). Proteolytic enzymes involved in MHC class I antigen processing: A guerrilla army that partners with the proteasome. Molecular immunology, 68(2 Pt A), 72-76. DOI:

Li, L., & Bouvier, M. (2004). Structures of HLA-A*1101 complexed with immunodominant nonamer and decamer HIV-1 epitopes clearly reveal the presence of a middle, secondary anchor residue. Journal of immunology (Baltimore, Md.: 1950), 172(10), 6175-6184. DOI:

Liao, Y., Cai, B., Li, Y., Chen, J., Ying, B., Tao, C., ... & Wang, L. (2015). Association of HLA‐DP/DQ, STAT 4 and IL‐28B variants with HBV viral clearance in Tibetans and Uygurs in China. Liver International, 35(3), 886-896. DOI:

Lin, W. H., Kouyos, R. D., Adams, R. J., Grenfell, B. T., & Griffin, D. E. (2012). Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics. Proceedings of the National Academy of Sciences of the United States of America, 109(37), 14989-14994. DOI: 10. 1073/pnas.1211138109

Locke, B., Semberg, E., Forsgren, E., & de Miranda, J. R. (2017). Persistence of subclinical deformed wing virus infections in honeybees following Varroa mite removal and a bee population turnover. PloS one, 12(7), e0180910. DOI:

Lu, X., Gibbs, J. S., Hickman, H. D., David, A., Dolan, B. P., Jin, Y., ... & Varma, R. (2012). Endogenous viral antigen processing generates peptide-specific MHC class I cell-surface clusters. Proceedings of the National Academy of Sciences, 109(38), 15407-15412.DOI:

Ly, S., Fortas, C., Duong, V., Benmarhnia, T., Sakuntabhai, A., Paul, R., ... & Tarantola, A. (2019). Asymptomatic Dengue Virus Infections, Cambodia, 2012-2013. Emerging infectious diseases, 25(7), 1354. DOI:

Malpica, J. M., Fraile, A., Moreno, I., Obies, C. I., Drake, J. W., & García-Arenal, F. (2002). The rate and character of spontaneous mutation in an RNA virus. Genetics, 162(4), 1505-1511.

McKiernan, S. M., Hagan, R., Curry, M., McDonald, G. S., Kelly, A., Nolan, N., ... & Kelleher, D. (2004). Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source. Hepatology, 40(1), 108-114. DOI:

Menendez, C. M., & Carr, D. (2017). Defining nervous system susceptibility during acute and latent herpes simplex virus-1 infection. Journal of neuroimmunology, 308, 43-49. DOI: jneuroim.2017.02.020

Meiring, T., Prozesky, L., Du Preez, E. R., & Verwoerd, D. J. (2011). The diagnosis and prevalence of persistent infection with bovine viral diarrhoea virus in South African feedlot cattle. The Onderstepoort journal of veterinary research, 78(1), 323. DOI:

Momburg, F., & Hengel, H. (2002). Corking the bottleneck: the transporter associated with antigen processing as a target for immune subversion by viruses. Current topics in microbiology and immunology, 269, 57-74. DOI:

Morens, D. M., Taubenberger, J. K., & Fauci, A. S. (2009). The persistent legacy of the 1918 influenza virus. The New England Journal of Medicine, 361(3), 225-229. DOI: 10.1056/NEJMp0904819

Mosaad, Y. M., Farag, R. E., Arafa, M. M., Eletreby, S., El-Alfy, H. A., Eldeek, B. S., & Tawhid, Z. M. (2010). Association of human leucocyte antigen Class I (HLA-A and HLA-B) with chronic hepatitis C virus infection in Egyptian patients. Scandinavian journal of immunology, 72(6), 548-553. DOI:

Nielsen, C. F., Reisen, W. K., Armijos, M. V., Maclachlan, N. J., & Scott, T. W. (2008). High subclinical West Nile virus incidence among nonvaccinated horses in northern California associated with low vector abundance and infection. The American journal of tropical medicine and hygiene, 78(1), 45-52. DOI: 10.4269/ajtmh.2008.78.45

Nishida, N., Sawai, H., Matsuura, K., Sugiyama, M., Ahn, S. H., Park, J. Y., ... & Mizokami, M. (2012). Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PloS one, 7(6), e39175. DOI:

Pan, N., Chen, K., Qiu, J., Sun, H., Xu, J., Miao, F., ... & Zhang, J. (2013). Human leukocyte antigen class I alleles and haplotypes associated with primary hepatocellular carcinoma in persistent HBV-infected patients. Human immunology, 74(6), 758-763. DOI:

Pasharawipas, T. (2011). Inducible viral receptor, A possible concept to induce viral protection in primitive immune animals. Virology Journal, 8, 326. DOI:

Piguet, V. (2005). Receptor modulation in viral replication: HIV, HSV, HHV-8 and HPV: same goal, different techniques to interfere with MHC-I antigen presentation. Current topics in microbiology and immunology, 285, 199-217. DOI:

Porter, K. R., Beckett, C. G., Kosasih, H., Tan, R. I., Alisjahbana, B., Rudiman, P. I. F., ... & Wuryadi, S. (2005). Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia. The American journal of tropical medicine and hygiene, 72(1), 60-66. DOI: 10.4269/ajtmh.2005.72.60

Provenzano, M., Panelli, M. C., Mocellin, S., Bracci, L., Sais, G., Stroncek, D. F., ... & Marincola, F. M. (2006). MHC–peptide specificity and T-cell epitope mapping: where immunotherapy starts. Trends in molecular medicine, 12(10), 465-472. DOI:

Ramezani, A., Aghakhani, A., Kalantar, E., Banifazl, M., Eslamifar, A., & Velayati, A. A. (2009). HLA-A *3303* and *3301 predispose patients to persistent hepatitis B infection. Journal of gastrointestinal and liver diseases: JGLD, 18(1), 117-118.

Robinson, J., Halliwell, J. A., Hayhurst, J. D., Flicek, P., Parham, P., & Marsh, S. G. (2015). The IPD and IMGT/HLA database: allele variant databases. Nucleic acids research, 43 (Database issue), D423-D431. DOI:

Roche, P. A., & Furuta, K. (2015). The ins and outs of MHC class II-mediated antigen processing and presentation. Nature reviews. Immunology, 15(4), 203-216. DOI:

Rock, K. L., Reits, E., & Neefjes, J. (2016). Present yourself! By MHC class I and MHC class II molecules. Trends in immunology, 37(11), 724-737. DOI:

Sobao, Y., Sugi, K., Tomiyama, H., Saito, S., Fujiyama, S., Morimoto, M., ... & Takiguchi, M. (2001). Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A* 2402, the most common HLA class I allele in East Asia. Journal of hepatology, 34(6), 922-929. DOI:

Sharma, S. K., Saini, N., & Chwla, Y. (2005). Hepatitis B virus: inactive carriers. Virology journal, 2, 82. DOI:

Shastri, N., Schwab, S., & Serwold, T. (2002). Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. Annual review of immunology, 20, 463-493. DOI:

Sritunyalucksana, K., Srisala, J., McColl, K., Nielsen, L., & Flegel, T.W. (2006). Comparison of PCR testing methods for white spot syndrome virus [WSSV] infections in penaeid shrimp. Aquaculture 255: 95-104. DOI:

Stone, J. D., Aggen, D. H., Chervin, A. S., Narayanan, S., Schmitt, T. M., Greenberg, P. D., & Kranz, D. M. (2011). Opposite effects of endogenous peptide-MHC class I on T cell activity in the presence and absence of CD8. Journal of immunology (Baltimore, Md.: 1950), 186(9), DOI: 5193-5200.

Teunis, P. F., Sukhrie, F. H., Vennema, H., Bogerman, J., Beersma, M. F., & Koopmans, M. P. (2015). Shedding of norovirus in symptomatic and asymptomatic infections. Epidemiology and infection, 143(8), 1710-1717. DOI:

Thenmozhi, V., Rajendran, R., Ayanar, K., Manavalan, R., & Tyagi, B. K. (2006). Long-term study of Japanese encephalitis virus infection in Anopheles subpictus in Cuddalore district, Tamil Nadu, South India. Tropical medicine & international health: TM & IH, 11(3), 288-293. DOI:

Walker, P. J., & Mohan, C. V. (2009). Viral disease emergence in shrimp aquaculture: origins, impact and the effectiveness of health management strategies. Reviews in aquaculture, 1(2), 125-154. DOI:

Yin, J. W., Ping Huang, M., & Zhong, B. (2016). Intrahepatic Toll-Like Receptor 3 in Chronic HBV Infection Subjects: Asymptomatic Carriers, Active Chronic Hepatitis, Cirrhosis, and Hepatocellular Carcinoma. Hepatitis monthly, 16(6), e34432. DOI: 10.5812/hepatmon.34432

Urabe, Y., Ochi, H., Kato, N., Kumar, V., Takahashi, A., Muroyama, R., ... & Matsuda, K. (2013). A genome-wide association study of HCV-induced liver cirrhosis in the Japanese population identifies novel susceptibility loci at the MHC region. Journal of hepatology, 58(5), 875-882. DOI:

WHO. (2020, July 27). Hepatitis B.

WHO. (2020, July 27). Hepatitis C.

Wooster, A. L., Anderson, T. S., & Lowe, D. B. (2019). Expression and characterization of soluble epitope-defined major histocompatibility complex (MHC) from stable eukaryotic cell lines. Journal of immunological methods, 464, 22-30. DOI:

Zambon, R. A., Vakharia, V. N., & Wu, L. P. (2006). RNAi is an antiviral immune response against a dsRNA virus in Drosophila melanogaster. Cellular microbiology, 8(5), 880-889. DOI: https://doi. org/10.1111/ j.1462-5822.2006.00688.x

Zhao, S. N., Liu, L. L., Lv, Z. P., Wang, X. H., & Wang, C. H. (2017). Network analysis of HBV‑ and HCV‑induced hepatocellular carcinoma based on Random Forest and Monte Carlo cross‑validation. Molecular medicine reports, 16(3), 2411-2416. DOI: 2017. 6861

Zhu, M., Dai, J., Wang, C., Wang, Y., Qin, N., Ma, H., ... & Hu, Z. (2016). Fine mapping the MHC region identified four independent variants modifying susceptibility to chronic hepatitis B in Han Chinese. Human molecular genetics, 25(6), 1225-1232. DOI:




How to Cite

Tirasak Pasharawipas, Khurawan Kumkrong, & Rungnapa Veeramano. (2023). Perspective concerning MHC molecules in viral persistence. Journal of Current Science and Technology, 11(2), 171–180. Retrieved from



Notes or Short Communications