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
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
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


Barry, M. A., Campos, S. K., Ghosh, D., Adams, K. E., Mok, H., Mercier, G. T., & Parrott, M. B. (2003). Biotinylated gene therapy vectors. Expert opinion on biological therapy, 3(6), 925-40.

The avidin-biotin system is a fundamental technology in biomedicine for immunolocalisation, imaging, nucleic acid blotting and protein labelling. This technology has recently been adapted for use in gene therapy vector applications to add proteins or cell-targeting ligands to non-viral and viral vectors. Two biotinylation technologies are being used in these applications: chemical biotinylation and metabolic biotinylation. In chemical biotinylation, reactive alkylating agents couple biotin to proteins by random covalent attachment to amino acid side chains. In metabolic biotinylation, proteins are genetically engineered with a biotin acceptor peptide (BAP), such that they are covalently biotinylated by cellular biotin ligases during viral vector production. Both technologies show promise for cell-targeting in vitro and in vivo, and for ligand screening applications. Metabolic biotinylation has the added feature of allowing viruses, vectors and vaccines to be produced from cells already biotinylated, thereby allowing them to purified by affinity chromatography on monomeric avidin columns.

Smith, J. L., Campos, S. K., & Ozbun, M. A. (2007). Human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes. Journal of virology, 81(18), 9922-31.

Papillomaviruses are species-specific and epitheliotropic DNA viruses that cause tumors in their natural hosts. Certain infections with genital human papillomavirus (HPV) types are causally related to cervical cancer development. Most papillomaviruses are thought to infect cells via a clathrin-dependent pathway, yet no studies have determined the entry route in permissive host epithelial cells. Employing fluorescently labeled and native virions, we tested the effects of dominant-negative and biochemical inhibitors of cellular endocytosis pathways. Infections of human keratinocytes, a natural host cell type for HPVs, were assessed visually and by infectious entry assays. We found that HPV type 31 (HPV31) entry and initiation of early infection events require both caveolin 1 and dynamin 2 and occur independently of clathrin-mediated endocytosis. Treatment with chlorpromazine and filipin had opposing effects on HPV31 and HPV16 infection. HPV31 entry was remarkably slow, with a half-time of approximately 14 h, whereas the entry half-time of HPV16 was 4 h. Consistent with a caveola-mediated entry pathway for HPV31, the virions associated with detergent-resistant lipid rafts. During a 16-h microscopic tracking of HPV31 and HPV16 virions, no colocalization of the two viral types was observed. These data suggest that HPV31 and HPV16 virions use distinct routes for host epithelial cell entry.

Smith, J. L., Campos, S. K., Wandinger-Ness, A., & Ozbun, M. A. (2008). Caveolin-1-dependent infectious entry of human papillomavirus type 31 in human keratinocytes proceeds to the endosomal pathway for pH-dependent uncoating. Journal of virology, 82(19), 9505-12.

High-risk human papillomaviruses (HPVs) are small nonenveloped DNA viruses with a strict tropism for squamous epithelium. The viruses are causative agents of cervical cancer and some head and neck cancers, but their differentiation-dependent life cycles have made them difficult to study in simple cell culture. Thus, many aspects of early HPV infection remain mysterious. We recently showed the high-risk HPV type 31 (HPV31) enters its natural host cell type via caveola-dependent endocytosis, a distinct mechanism from that of the closely related HPV16 (Smith et al., J. Virol. 81:9922-9931, 2007). Here, we determined the downstream trafficking events after caveolar entry of HPV31 into human keratinocytes. After initial plasma membrane binding, HPV31 associates with caveolin-1 and transiently localizes to the caveosome before trafficking to the early endosome and proceeding through the endosomal pathway. Caveosome-to-endosome transport was found to be Rab5 GTPase dependent. Although HPV31 capsids were observed in the lysosome, Rab7 GTPase was dispensable for HPV31 infection, suggesting that viral genomes escape from the endosomal pathway prior to Rab7-mediated capsid transport. Consistent with this, the acidic pH encountered by HPV31 within the early endosomal pathway induces a conformational change in the capsid resulting in increased DNase susceptibility of the viral genome, which likely aids in uncoating and/or endosomal escape. The entry and trafficking route of HPV31 into human keratinocytes represents a unique viral pathway by which the virions use caveolar entry to eventually access a low-pH site that appears to facilitate endosomal escape of genomes.

Wu, Y., Campos, S. K., Lopez, G. P., Ozbun, M. A., Sklar, L. A., & Buranda, T. (2007). The development of quantum dot calibration beads and quantitative multicolor bioassays in flow cytometry and microscopy. Analytical biochemistry, 364(2), 180-92.

The use of fluorescence calibration beads has been the hallmark of quantitative flow cytometry. It has enabled the direct comparison of interlaboratory data as well as quality control in clinical flow cytometry. In this article, we describe a simple method for producing color-generalizable calibration beads based on streptavidin functionalized quantum dots. Based on their broad absorption spectra and relatively narrow emission, which is tunable on the basis of dot size, quantum dot calibration beads can be made for any fluorophore that matches their emission color. In an earlier publication, we characterized the spectroscopic properties of commercial streptavidin functionalized dots (Invitrogen). Here we describe the molecular assembly of these dots on biotinylated beads. The law of mass action is used to readily define the site densities of the dots on the beads. The applicability of these beads is tested against the industry standard, namely commercial fluorescein calibration beads. The utility of the calibration beads is also extended to the characterization surface densities of dot-labeled epidermal growth factor ligands as well as quantitative indicators of the binding of dot-labeled virus particles to cells.

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.