Iron metabolism markers and haptoglobin phenotypes in susceptibility to HSV‐1 or/and HSV‐2 lesion relapses

Abstract

Different haptoglobin (Hp) phenotypes play a role in several pathologic processes including infectious diseases. In order to evaluate the role of iron storage and metabolism in susceptibility to herpetic manifestations, we studied the frequency of the Hp phenotypes and iron metabolism in patients affected by H. Simplex virus 1 or 2 (HSV-1 or HSV-2), compared with controls. Hp phenotype and iron metabolism were determined in 100 patients with recurrent HSV-1 or HSV-2 manifestations during the relapses, and in 110 healthy subjects. The frequencies of the three Hp phenotypes in the patient group compared to the control group were 18% versus 14.5% p = NS for Hp 1.1, 25% versus 40% p = 0.03 for Hp 2.2 and 57% versus 45.5% p = NS for Hp 2.1. All iron metabolism parameters tested showed significant differences between patients and controls; haemoglobin (Hb), ferritin, and serum iron were lower, while transferrin was higher in the patients than in controls. Reductions in iron availability may be a risk factor for relapsing lesions of HSV-1 or HSV-2. Hp 2.2 phenotype may offer some protection against the recurrence of Herpes labialis or genitalis manifestations.

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

“…The combinatorial aspect is important, since there are theoretical grounds, as well as abundant evidence, to the effect that several steps in a network must be modulated simultaneously to exhibit substantial effects (see e.g. Ágoston et al 2005; Ambesi-Impiombato and di Bernardo 2006; Bender et al 2006; Borisy et al 2003; Csermely et al 2005; Dancey and Chen 2006; Fan et al 2003, 2006; Haggarty et al 2003; Hopkins et al 2006; Kaelin 2005; Keith et al 2005; Kostoff and Delafuente 2006; Millan 2006; Perlstein et al 2006; Sharom et al 2004; Shiomi et al 1999; Wermuth 2004) (Brötz-Oesterhelt and Brunner 2008; Chong and Sullivan 2007; Costanzo et al 2010; Gerber et al 2007; Goltsov et al 2009; Hegreness et al 2008; Huang et al 2008b; Jia et al 2009; Koufaki et al 2009; Kuhn et al 2010; Lee et al 2007; Lehár et al 2007, 2008a, b; Li et al 2007; Liby et al 2007; Morphy and Rankovic 2007; Pachauri et al 2009; Reznichenko et al 2010; Sarkar and Li 2009; Sarkar et al 2009; Sawyers 2007; Schrattenholz and Šoškić 2008; Silver et al 2009; Silver 2007; Sporn et al 2007; Stommel et al 2007; Suchy et al 2009; Ulrich-Merzenich et al 2009; Watterson et al 2008; Weinreb et al 2009b; Whitehurst et al 2007; Wong et al 2008; Yeh et al 2006, 2009; Ying et al 2008; Zamin et al 2009; Zhang 2006; Zhang et al 2010; Zimmermann et al 2007). The same holds true for biotechnology (Kell and Westerhoff 1986a), in which typically we seek to maximise fluxes (Park et al 2007, 2008).…”

“…The above suggestions are certainly true of infections caused by influenza A (Visseren et al 2002) (see also Akaike et al 1996; Beck et al 2004), herpes simplex virus (Gennero et al 2010; Lamey and Biagioni 1995; Romeo et al 2001), hepatitis C (Alavian and Tabatabaei 2009; Alla and Bonkovsky 2005; Ameli et al 2008; Bassett 2007; Batts 2007; Bonkovsky 2002; Bonkovsky et al 2006; Desai et al 2008; Di Marco et al 2008; Drakesmith and Prentice 2008; Fargion et al 2002; Ferrara et al 2009; Franchini et al 2008; Fujita et al 2007a, b; Fujita and Takei 2007; Girelli et al 2009; Gürkan et al 2005; Guyader et al 2007; Hayashi and Yano 2002; Heathcote 2004; Kaito 2007; Kaito et al 2006; Kato et al 2001, 2007; Ko et al 2007; Mahmoud et al 2008; Mueller et al 2006; Nahon et al 2008; Nishina et al 2008; Otogawa et al 2008; Price and Kowdley 2009; Rigamonti et al 2005; Sebastiani and Walker 2007; Sikorska et al 2010; Sugimoto et al 2009; Tanaka et al 2007; Tanaka and Kiyosawa 2004; Trinder et al 2008; Tung et al 2003; Valenti et al 2008; Venturini et al 2010; Won et al 2009) and HIV (Boelaert et al 1996; Butensky James et al 2009; de Monyé et al 1999; Debebe et al 2007; Drakesmith and Prentice 2008; Georgiou et al 2000; Gordeuk et al 2001, 2006; Kagu et al 2007; Ketonen et al 1996; McDermid et al 2007; McDermid and Prentice 2006; McDermid et al 2009; Meyer 2006; Northrop-Clewes 2008; Rawat et al 2008; Savarino et al 1999; Schreck et al 1992; Szajerka and Jablecki …”

Serum Iron Parameters and Acute Experimental EHV‐1 Infection in Horses

“…The role of serum iron (sFe) status in microbial infections is recognized in both human and veterinary medicine . Mammalian hosts as well as most pathogens require iron (Fe) for vital metabolic functions such as the mitochondrial electron transport chain, phagocytosis, and oxygen transport.…”

“…Variations in Fe‐related proteins such as haptoglobin and transferrin may affect patient susceptibility and survival in microbial infections . An understanding of Fe metabolism in microbial disease has led to investigation of pathogen‐specific Fe‐related molecules as possible targets for prophylactic or therapeutic intervention.…”