About

Fenyong Liu is a Professor of Infectious Diseases at UC Berkeley Public Health. His research interests include the biology of human viruses such as herpes and cytomegalovirus, the development of novel antiviral agents, and the biochemistry of nucleic acids and RNA enzymes. He holds a PhD in Biochemistry & Molecular Biology from the University of Chicago, obtained in 1992, a Master's degree in Biochemistry & Molecular Biology from the same institution in 1989, and a Bachelor's degree in Biology from the University of Science and Technology, China, earned in 1986. His work focuses on understanding viral mechanisms and developing targeted antiviral therapies, contributing to the field of infectious diseases through his research and expertise.

Research topics

• Genetics
• Biology
• Virology
• Immunology
• Molecular biology
• Computational biology

Selected publications

• Recent Studies on Kaposi’s Sarcoma-Associated Herpesvirus Circular RNAs

  Cancers · 2025-11-23 · 2 citations

  reviewOpen accessSenior authorCorresponding

  Kaposi's sarcoma (KS), an AIDS-defining illness, is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). A member of the human herpesvirus family, designated as human herpesvirus 8 (HHV-8), KSHV is also linked to other oncogenic manifestations such as primary effusion lymphoma (PEL). The current dearth of available compounds against KSHV necessitates development of effective antiviral treatments. As with other herpesviruses, KSHV can result in both lytic and latent infections. KSHV pathogenesis and the development of KS have been associated with the expression of KSHV genes and transcripts during viral infections. The transcriptome of KSHV heavily intersects with regulatory pathways and mechanisms involved with a multitude of diseases in humans. Circular RNAs (circRNAs) have recently been discovered to be expressed by KSHV. Research endeavors on KSHV circRNAs have focused on the roles they play throughout latent and lytic infection. Understanding the specific functions and interactions of KSHV circRNAs with the viral and host transcriptomes, as well as how they are identified and analyzed, will be the primary focus of this review. Overall, recent advances in KSHV circRNA research have deepened our understanding of the KSHV transcriptome and pathogenesis and are paving the way for the development of circRNA-based antiviral therapies.

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• Effective Immune Protection of Mice from Murine Cytomegalovirus Infection by Oral Salmonella-Based Vaccine Expressing Viral M78 Antigen

  Vaccines · 2025-01-28 · 5 citations

  articleOpen accessSenior authorCorresponding

  Background: Human cytomegalovirus (CMV) is the most common cause of viral congenital infections worldwide. The development of effective vaccines against human CMV infection and disease is a high priority. Attenuated Salmonella are attractive oral vaccine vectors against human diseases because they can be administrated orally. Methods: In this study, an attenuated Salmonella strain was generated as an oral vaccine vector for the delivery and expression of the M78 protein of murine cytomegalovirus (MCMV). Using the MCMV infection of mice as the CMV infection model, we characterized the immune responses and protection induced by the constructed Salmonella-based vaccine. Results: The generated Salmonella-based vaccine, v-M78, which contained an M78 expression plasmid construct, carried out gene transfer efficiently for M78 expression and showed little pathogenicity and virulence in mice. In orally vaccinated mice, v-M78 induced anti-MCMV serum IgG and mucosal IgA responses and also elicited anti-MCMV T cell responses. Furthermore, mice immunized with v-M78 were protected from intraperitoneal and intranasal challenges with MCMV. The v-M78 vaccination reduced the titers of the challenged viruses in spleens, livers, lungs, and salivary glands. Conclusions: These results provide the first direct evidence that a Salmonella-based vaccine expressing M78 elicits strong humoral and cellular immune responses and induces immune protection against MCMV infection. Furthermore, our study demonstrates the potential of using Salmonella-based oral vaccines against CMV infection.

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• Applications of CRISPR-Cas-Based Genome Editing Approaches Against Human Cytomegalovirus Infection

  Biomedicines · 2025-06-30

  reviewOpen accessSenior authorCorresponding

  Human cytomegalovirus (HCMV), a globally ubiquitous herpesvirus with the ability to carry out both lytic productive and lifelong latent infections, is a major cause of congenital infections, often leading to intellectual disabilities and neurological disorders. Moreover, HCMV is an opportunistic pathogen commonly found in immunocompromised individuals such as organ transplant recipients, HIV-positive individuals, and cancer patients, causing severe and life-threatening complications. While effective in inhibiting viral lytic infection, current FDA-approved compounds cannot eliminate the latent viral genome and have little effect on viral latent infection. Developing novel antiviral therapeutic approaches to eliminate HCMV lytic and latent infections is a major public health priority for controlling HCMV infection and preventing viral-associated diseases. The genome-editing technology based on the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) RNA-guided nuclease system represents a novel and promising antiviral approach through modifying or destroying the genetic material of human viruses. This review summarizes the recently published progress in using the CRISPR-Cas approach to study and inhibit HCMV infections and discusses prospects for developing the CRISPR-based genome-editing technology for therapeutic applications against HCMV infection and associated diseases.

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• An Oral Salmonella-Based Vaccine Expressing Viral M43 Protein Elicits Effective Immunity Against Murine Cytomegalovirus in Mice

  Pathogens · 2025-09-08 · 1 citations

  articleOpen accessSenior authorCorresponding

  Human cytomegalovirus (HCMV) is the leading viral cause of congenital infections and causes substantial morbidity and mortality in neonates and immunosuppressed people. Generating an anti-HCMV vaccine is required for preventing viral-associated diseases and infections. Oral vaccines based on attenuated Salmonella are an attractive solution, since these vaccines can be applied orally and easily for mass immunization. In this report, we constructed an attenuated Salmonella strain for the expression of the murine cytomegalovirus (MCMV) M43 protein and studied its ability as an oral vaccine candidate to stimulate antiviral immunity in mice. In orally immunized mice, the constructed vaccine, Sal-M43, elicited both serum IgG and mucosal IgA levels as well as T cell responses that were specific against the MCMV M43 protein. Moreover, the Sal-M43 immunization substantially inhibited the viral growth and infection in various organs and tissues and offered complete immune protection against both intraperitoneal and intranasal MCMV challenges. Thus, the Salmonella-based vaccine expressing the M43 antigen is effective in inducing anti-MCMV immunity. These findings also reveal the promise of developing oral anti-CMV vaccines based on attenuated Salmonella vectors expressing different viral antigens.

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• Antiviral Immune Responses Against Murine Cytomegalovirus Induced by an Oral Salmonella-Based Vaccine Expressing Viral M33 Protein

  Microorganisms · 2025-06-28 · 2 citations

  articleOpen accessSenior authorCorresponding

  Human cytomegalovirus (CMV) is the leading cause of congenital infections, often leading to mental retardation and neurological disorders. It is a major public health priority to develop a vaccine for preventing and controlling human CMV infection. In this report, we generated an oral Salmonella-based vaccine to express the M33 protein of murine cytomegalovirus (MCMV) and investigated the anti-MCMV immune responses induced in mice immunized with this vaccine. Compared to those administered with phosphate-buffered saline (PBS) or a control vaccine without M33 expression, mice immunized with the vaccine expressing the M33 protein exhibited a remarkable induction of antiviral serum IgG and mucosal IgA humoral responses and a significant elicitation of antiviral T cell responses. Successful inhibition of viral growth in lungs, spleens, livers, and salivary glands was also found in the vaccinated animals compared to the PBS-treated animals or those immunized with the control vaccine without M33 expression. Furthermore, substantial protection against MCMV challenge was observed in mice immunized with the vaccine. Thus, Salmonella-based vaccine expressing MCMV M33 can induce anti-MCMV effective immune responses and protection. Our study implies that attenuated Salmonella expressing human CMV antigens, including its homologue to M33, may represent promising oral anti-CMV vaccine candidates.

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• RNase P-Associated External Guide Sequences Inhibit HIV-1 Infection by Shutting Down Human CCR5 Expression

  Receptors · 2025-02-17 · 1 citations

  articleOpen accessSenior authorCorresponding

  Background: External guide sequences (EGSs) are small RNA molecules capable of hybridizing to a target mRNA and rendering the target RNA susceptible to degradation by ribonuclease P (RNase P), a tRNA processing enzyme. Methods: In this study, natural tRNA-originated and engineered variant EGSs were constructed to target the mRNA encoding human CC-chemokine receptor 5 (CCR5), an HIV co-receptor. Results: The EGS variant was about 100-fold more efficient in inducing RNase P-mediated cleavage of the CCR5 mRNA sequence in vitro than a natural tRNA-derived EGS. Furthermore, the expressed variant and natural tRNA-originated EGSs decreased CCR5 expression by 98% and 73–77% and reduced infection by the CCR5-tropic HIVBa-L strain in cells by more than 900- and 50-fold, respectively. By contrast, cells expressing these EGSs exhibited no change in the expression of CXCR4, another HIV co-receptor, and showed no reduction in infection by the CXCR4-tropic HIVIIIB strain, which uses CXCR4 instead of CCR5 as the co-receptor. Thus, the EGSs specifically targeted CCR5 but not CXCR4. Conclusions: Our results demonstrate that EGSs are effective and specific in diminishing HIV infection and represent a novel class of gene-targeting agents for anti-HIV therapy.

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• An Engineered RNase P Ribozyme Effectively Reduces Human Coronavirus 229E Gene Expression and Growth in Human Cells

  Zoonotic Diseases · 2025-05-12

  articleOpen accessSenior authorCorresponding

  The human coronavirus 229E (HCoV-229E) is a member of the human coronavirus family that includes SARS-CoV-2, the causative agent of COVID-19. Developing antiviral strategies and compounds is crucial to treat and prevent HCoV-229E infections and the associated diseases. Ribozymes derived from ribonuclease P (RNase P) catalytic RNA represent a novel class of promising gene-targeting agents by cleaving their target mRNA and knocking down the expression of the target mRNA. However, it has not been reported whether RNase P ribozymes block the infection and replication of HCoV-229E. We report here the engineering of an anti-HCoV-229E RNase P ribozyme to target an overlapping region of viral genomic RNA and the mRNA encoding the nucleocapsid (N) protein, which is vital for viral replication and growth. The engineered ribozyme actively hydrolyzed the viral RNA target in vitro. HCoV-229E-infected cells expressing the engineered, catalytically active ribozyme exhibited a reduction of about 85% in viral RNA levels and N protein expression, and a reduction of about 750-fold in infectious particle production, compared to cells expressing no ribozymes or a control, catalytically inactive ribozyme. Our study provides the first direct evidence of the therapeutic potential of RNase P ribozymes against human coronaviruses such as HCoV-229E.

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• Congenital Human Cytomegalovirus and the Complement System

  Viruses · 2025-09-29 · 1 citations

  reviewOpen accessSenior authorCorresponding

  Congenital human cytomegalovirus (HCMV) infection is the most common vertically transmitted viral infection, and it affects 1 in 200 live births worldwide. While neonates are often asymptomatic at birth, congenital HCMV infection can result in long-term complications, including microcephaly, sensorineural hearing loss, and neurodevelopmental abnormalities. Developing antiviral strategies for the treatment and prevention of congenital HCMV infections is a global public health priority. However, licensed anti-HCMV vaccines are not yet available, and therapeutic options for use during pregnancy remain limited. The complement system is a crucial component of the innate immune system that plays essential roles in both fetal development and maternal defense against infectious pathogens. In cases of congenital HCMV infection, complement may contribute to the successful containment of the virus, but dysregulation and overactivation could concurrently drive tissue-damaging inflammation. This review discusses the known roles of the complement system in fetal development and in HCMV pathogenesis and synthesizes existing research to develop the hypothesis that a dysregulated complement system is a key mechanism in the development of congenital HCMV-related pathogenesis and neurodevelopmental sequelae. We explore how HCMV may perturb the complement system during pregnancy and use one inhibitor example to illustrate the broader potential of targeting complement in limiting disease.

  PublisherOA PDFDOI

• Engineering of highly active gene targeting RNase P ribozyme against human cytomegalovirus infection

  hLife · 2025-02-26 · 1 citations

  articleOpen accessSenior authorCorresponding

  Sequence-specific ribonuclease (RNase) P ribozymes can be engineered in vitro and are promising gene-targeting agents to knock down gene expression. In this study, we applied an RNase P ribozyme variant to hydrolyze the mRNA of human cytomegalovirus (HCMV) major capsid protein (MCP), which is necessary for viral capsid formation and growth. Functional variant R668-F was about 100 times more efficient in slicing the MCP mRNA in vitro than M1-F, the ribozyme with a natural RNase P ribozyme sequence. In R668-F-expressing cells, a decrease of about 98%–99% in the expression of MCP was detected, and the virus production was reduced by 70,000 folds. However, the expression of inactive control ribozymes in cells resulted in a less than 10% decrease in MCP expression and no apparent decrease in HCMV growth. In cells observed with the ribozyme-mediated reduction of MCP expression, HCMV capsid formation and virus growth were inhibited and the expressions of other viral genes were unaffected. These findings provide the first direct evidence that ribozyme R668-F specifically inhibits MCP expression and blocks HCMV growth. Our results further suggest that the engineered RNase P ribozymes, including R668-F, may act as a novel general gene-targeting strategy to treat infections of viruses, including HCMV. • An active sequence-specific ribozyme is engineered from ribonuclease (RNase) P catalytic RNA with novel mutations enhancing its activity. • The engineered RNase P ribozyme represents a gene-targeting agent by cleaving a target mRNA and reducing its expression. • The constructed ribozyme inhibits the major capsid protein expression of human cytomegalovirus and viral growth in cells.

  PublisherDOI

• The discovery of a catalytic RNA within RNase P and its legacy

  Journal of Biological Chemistry · 2024-04-25 · 14 citations

  reviewOpen accessCorresponding

  Sidney Altman's discovery of the processing of one RNA by another RNA that acts like an enzyme was revolutionary in biology and the basis for his sharing the 1989 Nobel Prize in Chemistry with Thomas Cech. These breakthrough findings support the key role of RNA in molecular evolution, where replicating RNAs (and similar chemical derivatives) either with or without peptides functioned in protocells during the early stages of life on Earth, an era referred to as the RNA world. Here, we cover the historical background highlighting the work of Altman and his colleagues and the subsequent efforts of other researchers to understand the biological function of RNase P and its catalytic RNA subunit and to employ it as a tool to downregulate gene expression. We primarily discuss bacterial RNase P-related studies but acknowledge that many groups have significantly contributed to our understanding of archaeal and eukaryotic RNase P, as reviewed in this special issue and elsewhere.

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Recent grants

• NIH Grant R01DE016813

  NIH · $1.3M · 2010

• NIH Grant R29GM054815

  NIH · $730k · 2002

• Persistent infection of human cytomegalovirus in oral mucosa

  NIH · $2.3M · 2015–2020

• NIH Grant R01AI043250

  NIH · $548k · 2002

• Human cytomegalovirus chromatin modifications in oral infection

  NIH · $2.3M · 2013–2019

Frequent coauthors

• Phong Trang

  University of California, Berkeley

  61 shared

• Sangwei Lu

  Yale University

  42 shared

• Hao Gong

  31 shared

• Yuan‐Chuan Chen

  University of California, Berkeley

  29 shared

• Hua Zhu

  Shanghai Jiao Tong University

  28 shared

• Ao Shen

  State Key Laboratory of Respiratory Disease

  22 shared

• Liu Yu-jun

  22 shared

• Gia-Phong Vu

  University of California, Berkeley

  20 shared