Samuel K Campos

Samuel K Campos

Associate Professor, BIO5 Institute
Associate Professor, Cancer Biology - GIDP
Associate Professor, Immunobiology
Associate Professor, Molecular and Cellular Biology
Primary Department
Department Affiliations
(520) 626-4842

Work Summary

Work Summary

We aim to understand the mechanisms of HPV infection, the cellular responses to HPV infection, and how the interplay between host and virus influences the outcome

Research Interest

Research Interest

Samuel Campos, PhD, studies early events of Human Papillomavirus (HPV) infection. HPVs are small, non-enveloped DNA viruses that cause a variety of lesions ranging from benign waters to cervical cancers. Although over 100 types of HPVs have been identified, HPV16 is the most prevalent, and is alone responsible for more than 50% of cervical cancers in women worldwide. Dr. Campos and his lab study the mechanisms of HPV virus transmission at a cellular level, in hopes to discover new approaches for the prevention and treatment of HPV.HPV16 virions consist of an ~8kb circular dsDNA genome packaged into a ~60 nm protein capsid. The genome is condensed with cellular histones and exists in a chromatin-like state. The capsid is comprised of 72 pentamers of the major capsid protein L1 and up to 72 molecules of the minor capsid protein L2, localized along the inner capsid surface, within the central cavities beneath the L1 pentamers. Mature HPV16 virions exist in an oxidized state, with adjacent L1 pentamers crosslinked together by disulfide bonds to stabilize the capsid. In order to establish an infection, HPV16 virions must bind and penetrate host cells, ultimately delivering their genomes to the host cell nucleus to initiate early gene expression, cell cycle progression, and genome replication. Non-enveloped viruses are faced with the challenge of getting their genetic material across a cellular membrane and often overcome this by disrupting the endosomal or lysosomal membranes and translocating to the cellular cytoplasm during the course of intracellular virion trafficking. Keywords: virology, microbiology, virus-host interaction, HPV


Frietze, K. M., Campos, S. K., & Kajon, A. E. (2012). No evidence of a death-like function for species B1 human adenovirus type 3 E3-9K during A549 cell line infection. BMC research notes, 5, 429.

Subspecies B1 human adenoviruses (HAdV-B1) are prevalent respiratory pathogens. Compared to their species C (HAdV-C) counterparts, relatively little work has been devoted to the characterization of their unique molecular biology. The early region 3 (E3) transcription unit is an interesting target for future efforts because of its species-specific diversity in genetic content among adenoviruses. This diversity is particularly significant for the subset of E3-encoded products that are membrane glycoproteins and may account for the distinct pathobiology of the different human adenovirus species. In order to understand the role of HAdV-B-specific genes in viral pathogenesis, we initiated the characterization of unique E3 genes. As a continuation of our efforts to define the function encoded in the highly polymorphic ORF E3-10.9K and testing the hypothesis that the E3-10.9K protein orthologs with a hydrophobic domain contribute to the efficient release of viral progeny, we generated HAdV-3 mutant viruses unable to express E3-10.9K ortholog E3-9K and examined their ability to grow, disseminate, and egress in cell culture.

Campos, S. K., & Barry, M. A. (2006). Comparison of adenovirus fiber, protein IX, and hexon capsomeres as scaffolds for vector purification and cell targeting. Virology, 349(2), 453-62.

The direct genetic modification of adenoviral capsid proteins with new ligands is an attractive means to confer targeted tropism to adenoviral vectors. Although several capsid proteins have been reported to tolerate the genetic fusion of foreign peptides and proteins, direct comparison of cell targeting efficiencies through the different capsomeres has been lacking. Likewise, direct comparison of with one or multiple ligands has not been performed due to a lack of capsid-compatible ligands available for retargeting. Here we utilize a panel of metabolically biotinylated Ad vectors to directly compare targeted transduction through the fiber, protein IX, and hexon capsomeres using a variety of biotinylated ligands including antibodies, transferrin, EGF, and cholera toxin B. These results clearly demonstrate that cell targeting with a variety of high affinity receptor-binding ligands is only effective when transduction is redirected through the fiber protein. In contrast, protein IX and hexon-mediated targeting by the same set of ligands failed to mediate robust vector targeting, perhaps due to aberrant trafficking at the cell surface or inside targeted cells. These data suggest that vector targeting by genetic incorporation of high affinity ligands will likely be most efficient through modification of the adenovirus fiber rather than the protein IX and hexon capsomeres. In contrast, single-step monomeric avidin affinity purification of Ad vectors using the metabolic biotinylation system is most effective through capsomeres like protein IX and hexon.

Frietze, K. M., Campos, S. K., & Kajon, A. E. (2010). Open reading frame E3-10.9K of subspecies B1 human adenoviruses encodes a family of late orthologous proteins that vary in their predicted structural features and subcellular localization. Journal of virology, 84(21), 11310-22.

Subspecies B1 human adenoviruses (HAdV-B1s) are important causative agents of acute respiratory disease, but the molecular bases of their distinct pathobiology are still poorly understood. Marked differences in genetic content between HAdV-B1s and the well-characterized HAdV-Cs that may contribute to distinct pathogenic properties map to the E3 region. Between the highly conserved E3-19K and E3-10.4K/RIDα open reading frames (ORFs), and in the same location as the HAdV-C ADP/E3-11.6K ORF, HAdV-B1s carry ORFs E3-20.1K and E3-20.5K and a polymorphic third ORF, designated E3-10.9K, that varies in the size of its predicted product among HAdV-B1 serotypes and genomic variants. As an initial effort to define the function of the E3-10.9K ORF, we carried out a biochemical characterization of E3-10.9K-encoded orthologous proteins and investigated their expression in infected cells. Sequence-based predictions suggested that E3-10.9K orthologs with a hydrophobic domain are integral membrane proteins. Ectopically expressed, C-terminally tagged (with enhanced green fluorescent protein [EGFP]) E3-10.9K and E3-9K localized primarily to the plasma membrane, while E3-7.7K localized primarily to a juxtanuclear compartment that could not be identified. EGFP fusion proteins with a hydrophobic domain were N and O glycosylated. EGFP-tagged E3-4.8K, which lacked the hydrophobic domain, displayed diffuse cellular localization similar to that of the EGFP control. E3-10.9K transcripts from the major late promoter were detected at late time points postinfection. A C-terminally hemagglutinin-tagged version of E3-9K was detected by immunoprecipitation at late times postinfection in the membrane fraction of mutant virus-infected cells. These data suggest a role for ORF E3-10.9K-encoded proteins at late stages of HAdV-B1 replication, with potentially important functional implications for the documented ORF polymorphism.

Campos, S., Calton, C. M., Schlegel, A. M., Chapman, J. A., & Campos, S. K. (2013). Human papillomavirus type 16 does not require cathepsin L or B for infection. The Journal of general virology, 94(Pt 8).

Cathepsin L (CatL) and cathepsin B (CatB) are lysosomal proteases that many viruses utilize for capsid disassembly. We tested whether CatL and CatB are required for infection by human papillomavirus type 16 (HPV16). CatL- and CatB-deficient mouse embryonic fibroblasts had higher levels of infection when compared with wild-type cells. Similar results were obtained in HaCaT keratinocytes treated with CatL- or CatB-specific small interfering RNA. Thus, CatL and CatB are not required for HPV16 infection but instead appear to restrict infection.

Campos, S. K., Chapman, J. A., Deymier, M. J., Bronnimann, M. P., & Ozbun, M. A. (2012). Opposing effects of bacitracin on human papillomavirus type 16 infection: enhancement of binding and entry and inhibition of endosomal penetration. Journal of virology, 86(8), 4169-81.

Cell invasion by human papillomavirus type 16 (HPV16) is a complex process relying on multiple host cell factors. Here we describe an investigation into the role of cellular protein disulfide isomerases (PDIs) by studying the effects of the commonly used PDI inhibitor bacitracin on HPV16 infection. Bacitracin caused an unusual time-dependent opposing effect on viral infection. Enhanced cellular binding and entry were observed at early times of infection, while inhibition was observed at later times postentry. Bacitracin was rapidly taken up by host cells and colocalized with HPV16 at late times of infection. Bacitracin had no deleterious effect on HPV16 entry, capsid disassembly, exposure of L1/L2 epitopes, or lysosomal trafficking but caused a stark inhibition of L2/viral DNA (vDNA) endosomal penetration and accumulation at nuclear PML bodies. γ-Secretase has recently been implicated in the endosomal penetration of L2/vDNA, but bacitracin had no effect on γ-secretase activity, indicating that blockage of this step occurs through a γ-secretase-independent mechanism. Transient treatment with the reductant β-mercaptoethanol (β-ME) was able to partially rescue the virus from bacitracin, suggesting the involvement of a cellular reductase activity in HPV16 infection. Small interfering RNA (siRNA) knockdown of cellular PDI and the related PDI family members ERp57 and ERp72 reveals a potential role for PDI and ERp72 in HPV infection.